ascorbic-acid and Atherosclerosis

Atherosclerosis is a pro-oxidative and pro-inflammatory disease state, which is the underlying cause of most cardiovascular events, estimated to affect 5.2% of the Australian population. Diet, and specifically vitamin C, through its antioxidant properties can play a role in impeding the development and progression of atherosclerosis. This systematic review conducted comprehensive searches in Medline, Emcare, Scopus, PubMed, and Cochrane using key search terms for vitamin C, plasma vitamin C, supplementation, and cardiovascular disease (CVD). The results demonstrated that vitamin C supplementation resulted in a significant increase in vitamin C levels in populations with or without CVD, except for one study on the CVD population. It was also seen that the healthy population baseline and post-intervention vitamin C levels were high compared to the CVD population. However, further research is indicated for CVD population groups with varying baseline vitamin C levels, such as low baseline vitamin C, within a more representative elderly cohort in order to formulate and update vitamin C repletion guidelines.

Topics: Antioxidants; Ascorbic Acid; Atherosclerosis; Cardiovascular Diseases; Diet; Dietary Supplements; Eating; Female; Heart Disease Risk Factors; Humans; Male; Middle Aged; Nutritional Status

For decades, there has been epidemiologic evidence linking chronic toxic metal exposure with cardiovascular disease, suggesting a therapeutic role for metal chelation. Given the lack of compelling scientific evidence, however, the indications for metal chelation were never clearly defined. To determine the safety and efficacy of chelation therapy, the National Institutes of Health funded the Trial to Assess Chelation Therapy (TACT). TACT was the first double-blind, randomized, controlled trial to demonstrate an improvement in cardiovascular outcomes with edetate disodium therapy in patients with prior myocardial infarction. The therapeutic benefit was striking among the prespecified subgroup of patients with diabetes.. We review the published literature focusing on the atherogenic nature of diabetes, as well as available evidence from clinical trials, complete and in progress, of metal chelation with edetate disodium therapy in patients with diabetes.. The TACT results support the concept that ubiquitous toxic metals such as lead and cadmium may be modifiable risk factors for cardiovascular disease, particularly in patients with diabetes.. The purpose of this review is to discuss the potential mechanisms unifying the pathogenesis of atherogenic factors in diabetes with toxic metal exposure, and the potential role of metal chelation.

Topics: Antioxidants; Arsenic; Ascorbic Acid; Atherosclerosis; Cadmium; Calcium Chelating Agents; Cardiovascular Diseases; Chelating Agents; Chelation Therapy; Copper; Diabetes Complications; Diabetes Mellitus; Edetic Acid; Glycation End Products, Advanced; Hospitalization; Humans; Iron; Lead; Lipid Metabolism; Mercury; Myocardial Infarction; Myocardial Revascularization; Oxidative Stress; Randomized Controlled Trials as Topic; Stroke

Consumption of plant sterols/ stanols has long been demonstrated to reduce plasma cholesterol levels. The objective of this review is to demonstrate the lipid-lowering activity and anti-atherogenic effects of natural and semi-synthetic plant sterols/ stanols based on evidence from cell-culture studies, animal studies and clinical trials. Additionally, this review highlights certain molecular mechanisms by which plant sterols/ stanols lower plasma cholesterol levels with a special emphasis on factors that affect the cholesterol-lowering activity of plant sterols/stanols. The crystalline nature and the poor oil solubility of these natural products could be important factors that limit their cholesterol-lowering efficiency. Several attempts have been made to improve the cholesterol-lowering activity by enhancing the bioavailability of crystalline sterols and stanols. Approaches involved reduction of the crystal size and/or esterification with fatty acids from vegetable or fish oils. However, the most promising approach in this context is the chemical modification of plant sterols /stanols into water soluble disodium ascorbyl phytostanyl phosphates analogue by esterification with ascorbic acid. This novel semi-synthetic stanol derivative has improved efficacy over natural plant sterols/ stanols and can provide additional benefits by combining the cholesterol-lowering properties of plant stanols with the antioxidant potential of ascorbic acid. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Topics: Animals; Anticholesteremic Agents; Ascorbic Acid; Atherosclerosis; Cholesterol; Humans; Lipids; Phytosterols; Phytotherapy; Solubility

Observational studies indicate that higher vitamin C intake is associated with reduced risk for cardiovascular diseases. However, randomised controlled trials (RCT) examining the effect of vitamin C on endothelial function (EF) have reported inconsistent results. The aims of this systematic review and meta-analysis were to determine the effect of vitamin C supplementation on EF and to investigate whether the effect was influenced by health status, study duration, dose and route of vitamin C administration.. We searched the Medline, Embase, Cochrane Library, and Scopus databases from inception to May 2013 for studies that met the following criteria: 1) RCT with adult participants, 2) vitamin C administered alone, 3) studies that quantified EF using commonly applied methods including ultrasound, plethysmography and pulse wave analysis.. Pooling the data from 44 clinical trials showed a significant positive effect of vitamin C on EF (SMD: 0.50, 95% CI: 0.34, 0.66, P < 0.001). Stratification of the analysis by health outcome revealed improved EF in atherosclerotic (SMD: 0.84, 95% CI: 0.41, 1.26, P < 0.001), diabetic (SMD: 0.52, 95% CI: 0.21, 0.82, P < 0.001) and heart failure patients (SMD: 0.48, 95% CI: 0.08, 0.88, P < 0.02) after vitamin C supplementation. The effect size appeared to be unaffected by study design, duration, baseline plasma vitamin C concentration or route of administration of vitamin C. The meta-regression showed a significant positive association between vitamin C dose and improvement in EF (β: 0.00011, 95% CI: 0.00001, 0.00021, P = 0.03).. Vitamin C supplementation improved EF. The effect of vitamin C supplementation appeared to be dependent on health status, with stronger effects in those at higher cardiovascular disease risk. PROSPERO Database registration: CRD42013004567, http://www.crd.york.ac.uk/prospero/

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Atherosclerosis; Cardiovascular Diseases; Dietary Supplements; Endothelium; Female; Healthy Volunteers; Humans; Inflammation; Male; Middle Aged; Randomized Controlled Trials as Topic; Regression Analysis; Young Adult

Atherosclerotic cardiovascular diseases (CVD) are a major source of mortality and morbidity in the general population. Oxidative modification of low-density lipoprotein cholesterol (LDL-C) represents the most important determinant factor in the development and progression of atherosclerotic lesions. Oxidative damage and the production of free radicals (FRs) in the endothelium are some of the main factors involved in the pathogenesis of the atherosclerotic process that causes CVD. Appropriate nutritional practices are of central importance in managing risk and treatment of CVD; in fact, many current guidelines for a healthy general population contain nutritional recommendations to reduce the risk of these diseases. Observational studies of vitamins C and E, the most prevalent natural antioxidant vitamins, suggest that supplemental use of these vitamins may lower the risk for coronary events. Despite these data, several large, randomized controlled trials have failed to confirm the benefits of vitamin C and E in cardiovascular prevention. The aim of this review is to examine the published studies regarding the effect of vitamins (C and E) and beta-carotene supplementation in the prevention of CVD due to atherosclerosis.

Topics: Antioxidants; Ascorbic Acid; Atherosclerosis; Cardiovascular Diseases; Carotenoids; Dietary Supplements; Humans; Oxidative Stress; Vitamin E

Chronic inflammation is a pathogenic feature of atherosclerosis and cardiovascular disease mediated by substances including angiotensin II, proinflammatory cytokines, and free fatty acids. This promotes generation of reactive oxygen species in vascular endothelial cells and smooth muscle cells, which mediate injury through several mechanisms. Reciprocal relationships between endothelial dysfunction and insulin resistance as well as cross-talk between hyperlipidaemia and the renin-angiotensin-aldosterone system (RAAS) at multiple levels contribute importantly to a variety of risk factors. Therefore, combination therapy that simultaneously addresses multiple mechanisms for the pathogenesis of atherosclerosis is an attractive emerging concept for slowing progression of atherosclerosis. Combined therapy with statins, peroxisome proliferator-activated receptors, and RAAS blockade demonstrates additive beneficial effects on endothelial dysfunction and insulin resistance when compared with monotherapies in patients with cardiovascular risk factors due to both distinct and interrelated mechanisms. These additive beneficial effects of combined therapies are consistent with laboratory and recent clinical studies. Thus, combination therapy may be an important paradigm for treating and slowing progression of atherosclerosis, coronary heart disease, and co-morbid metabolic disorders characterized by endothelial dysfunction and insulin resistance.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Atherosclerosis; Calcium Channel Blockers; Cardiovascular Agents; Drug Therapy, Combination; Endothelium, Vascular; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Insulin Resistance; NADPH Oxidases; Oxidative Stress; Peroxisome Proliferator-Activated Receptors; Reactive Oxygen Species; Renin-Angiotensin System; Treatment Outcome; Vitamin E

Macrophage cells within inflammatory lesions are exposed to a wide range of degrading and cytotoxic molecules including reactive oxygen species. Unlike neutrophils, macrophages do not normally die in this environment but continue to generate oxidants, phagocytose cellular remains, and release a range of cyto-active agents which modulate the immune response. It is this potential of the macrophage cell to survive in an oxidative environment that allows the growth and complexity of advanced atherosclerotic plaques. This review will examine the oxidants encountered by macrophages within an atherosclerotic plaque and describe some of the potential antioxidant mechanisms which enable macrophages to function within inflammatory lesions. Ascorbate, a-tocopherol, and glutathione appear to be central to the protection of macrophages yet additional antioxidant mechanisms appear to be involved. Gamma-Interferon causes macrophages to generate 7,8-dihydroneopterin, neopterin and 3-hydroxyanthranilic acid both of which have antioxidant properties. Manganese superoxide dismutase is also upregulated in macrophages. The evidence that these antioxidants provide further protection, so allowing the macrophage cells to survive within sites of chronic inflammation such as atherosclerotic plaques, will be described.

Topics: 3-Hydroxyanthranilic Acid; Antioxidants; Ascorbic Acid; Atherosclerosis; Cell Death; Glutathione; Humans; Macrophages; Neopterin; Oxidants; Superoxide Dismutase; Superoxides; Vitamin E

Vitamin C is a pivotal redox modulater in many biological reactions of which several remain poorly understood. Naturally, vitamin C has been the subject of many investigations over the past decades in relation to its possible beneficial effects on cardiovascular disease primarily based on its powerful yet general antioxidant properties. However, growing epidemiological, clinical and experimental evidence now suggests a more specific role of ascorbate in vasomotion and in the prevention of atherosclerosis. For example, in contrast to most other biological antioxidants, administration of vitamin C can apparently induce vasodilation. Millions of people worldwide can be diagnosed with vitamin C deficiency according to accepted definitions. In this perspective, the present review examines the evidence for a specific link between vitamin C deficiency and increased risk of atherosclerosis as well as the possible mechanisms by which vitamin C may exert its protective function.

Topics: Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Atherosclerosis; Coenzymes; Disease Models, Animal; Dyslipidemias; Endothelium, Vascular; Humans; Lipid Metabolism; Lipids; Nitric Oxide; Nitric Oxide Synthase; Scurvy; Vasodilation

Despite decreases in atherosclerotic coronary vascular disease over the last several decades, atherosclerosis remains a major cause of mortality in developed nations. One possible contributor to this residual risk is oxidant stress, which is generated by the inflammatory response of atherosclerosis. Although there is a wealth of in vitro, cellular, and animal data supporting a protective role for antioxidant vitamins and nutrients in the atherosclerotic process, the best clinical trials have been negative. This may be due to the fact that antioxidant therapies are applied "too little and too late." This review considers the role of vitamin C, or ascorbic acid in preventing the earliest inflammatory changes in atherosclerosis. It focuses on the three major vascular cell types involved in atherosclerosis: endothelial cells, vascular smooth muscle cells, and macrophages. Ascorbate chemistry, recycling, and function are described for these cell types, with emphasis on whether and how the vitamin might affect the inflammatory process. For endothelial cells, ascorbate helps to prevent endothelial dysfunction, stimulates type IV collagen synthesis, and enhances cell proliferation. For vascular smooth muscle cells, ascorbate inhibits dedifferentiation, recruitment, and proliferation in areas of vascular damage. For macrophages, ascorbate decreases oxidant stress related to their activation, decreases uptake and degradation of oxidized LDL in some studies, and enhances several aspects of their function. Although further studies of ascorbate function in these cell types and in novel animal models are needed, available evidence generally supports a salutary role for this vitamin in ameliorating the earliest stages of atherosclerosis.

Topics: Animals; Ascorbic Acid; Atherosclerosis; Endothelial Cells; Humans; Macrophages; Muscle, Smooth, Vascular; Nutritional Requirements

The clinical use of antioxidants has gained considerable interest during the last decade. It was suggested from epidemiological studies that diets high in fruits and vegetables might help decrease the risk of cardiovascular disease. Therefore, supplements of vitamins C and E were applied through protocols aimed to prevent diseases such as atherosclerosis, preeclampsia or hypertension, thought to be mediated by oxidative stress. Despite the biological properties of these vitamins could account for an effective protection, as shown by several clinical and experimental studies, their efficacy remains controversial in the light of some recent clinical trials and meta-analyses. However, the methodology of these studies, criteria for selection of patients, the uncertain extent of progression of the disease when initiating supplementation, the lack of mechanistic studies containing basic scientific aspects, such as the bioavailability, pharmacokinetic properties, and the nature of the antioxidant sources of vitamins, could account for the inconsistency of the various clinical trials and meta-analyses assessing the efficacy of these vitamins to prevent human diseases. This review presents a survey of the clinical use of antioxidant vitamins E and C, proposing study models based on the biological effects of these compounds likely to counteract the pathophysiological mechanisms able to explain the structural and functional organ damage.

Topics: Antioxidants; Ascorbic Acid; Atherosclerosis; Female; Humans; Hypertension; Models, Biological; Oxidative Stress; Pre-Eclampsia; Pregnancy; Vitamin E; Vitamins

NO produced by eNOS (endothelial nitric oxide synthase) is a key mediator of vascular homoeostasis. NO bioavailability is reduced early in vascular disease states, such as hypercholesterolaemia, diabetes and hypertension, and throughout the progression of atherosclerosis. This is a result of both reduced NO synthesis and increased NO consumption by reactive oxygen species. eNOS enzymatic activity appears to be determined by the availability of its cofactor BH4 (tetrahydrobiopterin). When BH4 levels are adequate, eNOS produces NO; when BH4 levels are limiting, eNOS becomes enzymatically uncoupled and generates superoxide, contributing to vascular oxidative stress and endothelial dysfunction. BH4 bioavailability is determined by a balance of enzymatic de novo synthesis and recycling, versus oxidative degradation in dysfunctional endothelium. Augmenting vascular BH4 levels by pharmacological supplementation, by enhancing the rate of de novo biosynthesis or by measures to reduce BH4 oxidation have been shown in experimental studies to enhance NO bioavailability. Thus BH4 represents a potential therapeutic target for preserving eNOS function in vascular disease.

Topics: Animals; Ascorbic Acid; Atherosclerosis; Biopterins; Disease Progression; Endothelium, Vascular; Homeostasis; Humans; Nitric Oxide; Nitric Oxide Synthase Type III; Oxidation-Reduction; Reactive Oxygen Species; Vitamins

Oxidative reactions caused by cigarette smoke (CS) chemicals have been shown to initiate crucial events in atherogenesis. However, physicians and scientists are confronted with the paradoxical situation that an antioxidative treatment of smokers improves acute smoking effects but hardly has any impact on long term outcome of cardiovascular diseases (CVD). In this review we make an attempt to explain this paradox. First, smoke-derived free radicals and oxidants are part of CS causing a pro-oxidative state in the circulatory system. Further, smoke chemicals down-regulate antioxidant defence enzymes that would counteract the oxidative burden by cigarette smoke. With the prolonged exposure to smoke, oxidation catalysing metals accumulate in the vessel wall and mediate local oxidation reactions. Therefore, pharmacological intervention relying on non-selective antioxidants often appears to be ineffective. Consequently a novel strategy for the prevention and treatment of CVD caused by smoking is suggest, relying on a combined application of antioxidants, substitution of factors important for physiological oxidant defence, and metal-detoxifying agents.

Topics: Antioxidants; Ascorbic Acid; Atherosclerosis; Calcium; Cardiovascular Diseases; Humans; Inflammation; Oxidants; Oxidative Stress; Smoking; Vitamin E

The studies on experimental animals (guinea pigs, monkeys, fish) have confirmed the important role of ascorbic acid deficiency in the development of hypercholesterolemia and atherosclerosis, but the clinical experience is not quite uniform. Metaanalyses of randomized controlled trials performed on subjects without established vitamin C-deficiency conclud that the evidence of the presence or absence of benefits derived from the ability of ascorbic acid to prevent cardiovascular diseases is not sufficient. This review is an outline of numerous clinical, epidemiological and prospective studies that have found a positive role of vitamin C in the prevention of atherosclerosis. If we admit the possibility that vitamin C deficiency is a significant risk factor of atherogenesis, due to ethical reasons it is impossible to perform long-term controlled trials on subjects with proved vitamin C deficiency, to recommend them not to change their nutrition and lifestyle, and to administer placebo to the control group. Therefore the proof of atherogenic effect of chronic vitamin C deficiency is limited to indirect evidence only. In this review many new data on the positive effects of ascorbic acid on human cardiovascular system are summarized and the mechanisms of its protective influence on blood vessels are discussed (Fig.5, Ref. 45). Full Text (Free, PDF) www.bmj.sk.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Atherosclerosis; Cardiovascular Diseases; Humans; Risk Factors

The generation by genetic engineering of two murine models to investigate atherosclerosis, such as the apoE- and LDLr- deficient mice, is providing an extraordinaire knowledge of the effect of different nutrients on this complex disease. The present revision provides a comprehensive overview of the advances in this field that point to a remarkable complexity. While some controversies over puzzling results could be explained invoking potential nutrient interactions or different food sources of nutrients, it also appears that other factors such as sex, genetic background or immunological status are emerging as generators of differential responses to nutrients during the atherosclerotic process.

Topics: Alcohol Drinking; Allergy and Immunology; Animals; Antioxidants; Apolipoproteins E; Arginine; Arteriosclerosis; Ascorbic Acid; Atherosclerosis; Cell Proliferation; Dietary Fats; Disease Models, Animal; Energy Metabolism; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Genetic Engineering; Genetic Variation; Genomics; Homocysteine; Insulin Resistance; Iron; Magnesium; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Biological; Models, Genetic; Phytosterols; Receptors, LDL; Sex Factors; Sodium; Taurine; Vitamin E

Peripheral vascular disease (PVD) is a manifestation of systemic atherosclerosis in the lower limbs, and PVD patients have a 3- to 5-fold increased risk of cardiovascular mortality compared with age-matched controls. Nevertheless, recent reports show how PVD patients are undertreated with regard to CVD risk-factor reduction and the use of lipid-lowering or antiplatelet drugs. There is appreciable evidence that demonstrates the beneficial effects of certain nutrients and dietary habits in the prevention of CVD, but there has been little attention paid to the role of nutrients in PVD. The purpose of the present review is to provide an overview of our understanding of how foods could possibly benefit PVD. In the last few decades, several nutrients have arisen as potentially health-promoting in PVD. While nutritional interventions in PVD show positive clinical effects for fish oil, carnitine or vitamin E, others such as olive oil or vitamin C seem to interact only at a biochemical level by decreasing risk factors. Moreover, only epidemiological associations exist for the potential role of fibre, folates or vitamin B6 in this disease. In all cases, the limited data available provide no clear-cut evidence in favour of the clinical benefit of nutritional interventions aimed at reducing risk factors and ameliorating symptoms in PVD patients. No practical recommendations can be given at this stage, and further studies are clearly needed.

Topics: Antioxidants; Ascorbic Acid; Atherosclerosis; Carnitine; Dietary Fats, Unsaturated; Dietary Fiber; Fish Oils; Humans; Nutritional Physiological Phenomena; Olive Oil; Peripheral Vascular Diseases; Plant Oils; Vitamin B Complex; Vitamin E

In vitro studies have shown that antioxidants (e. g. beta-carotene, vitamin C and vitamin E) can interfere with some pathomechanisms of atherosclerosis and therefore might have a protective effect. From the investigated antioxidants vitamin E showed the best effect. Some animal and epidemiological studies confirmed such a protective effect in vivo especially after administration of high doses of vitamin E. However, most of the placebo-controlled studies for primary or secondary prevention failed to show a protective effect even after administration of high doses. In addition, other studies demonstrated a risk for adverse effects due to antioxidant supplementation (beta-carotene and vitamin E). Our review summarises the principle of antioxidant supplementation and a number of relevant epidemiological and clinical studies for prevention of atherosclerosis. The obtained results suggest that supplementation of antioxidants cannot be recommended for the normal population.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Animals; Anticholesteremic Agents; Antioxidants; Ascorbic Acid; Atherosclerosis; beta Carotene; Case-Control Studies; Dietary Supplements; Female; Follow-Up Studies; Humans; Male; Meta-Analysis as Topic; Middle Aged; Oxidants; Primary Prevention; Probucol; Prospective Studies; Randomized Controlled Trials as Topic; Reactive Oxygen Species; Risk; Risk Factors; Sex Factors; Time Factors; Tocopherols; Vitamin E; Vitamins

Laboratory and observational studies suggest that antioxidant and B vitamin supplementation may prevent atherosclerosis. Although trials have not shown a benefit of these supplements on clinical cardiovascular events, it is unknown whether they affect the progression of atherosclerosis as measured by imaging techniques.. The objective was to perform a meta-analysis of randomized controlled trials of the effect of vitamin-mineral supplementation on atherosclerosis progression.. We searched the MEDLINE, EMBASE, and CENTRAL databases for relevant studies. No language restrictions were applied. We separately analyzed trials using antioxidants (vitamins E and C, beta-carotene, or selenium) and trials using B vitamins (folate, vitamin B-6, or vitamin B-12). The progression of atherosclerosis was evaluated by B-mode ultrasound, intravascular ultrasound, or angiography. Effect sizes were calculated for the difference in slope of atherosclerosis progression between participants assigned to supplements and those assigned to the control group.. In trials not involving percutaneous transluminal coronary angioplasty, the pooled effect size was -0.06 (95% CI: -0.20, 0.09; 7 trials) for antioxidants and -0.93 (95% CI: -2.11, 0.26; 4 trials) for B vitamins. In trials involving percutaneous transluminal coronary angioplasty, the pooled relative risk of restenosis was 0.82 (95% CI: 0.54, 1.26; 3 trials) for antioxidants and 0.84 (95% CI: 0.34, 2.07; 2 trials) for B vitamins.. Our meta-analysis showed no evidence of a protective effect of antioxidant or B vitamin supplements on the progression of atherosclerosis, thus providing a mechanistic explanation for their lack of effect on clinical cardiovascular events.

Topics: Adult; Aged; Angiography; Angioplasty, Balloon, Coronary; Antioxidants; Ascorbic Acid; Atherosclerosis; beta Carotene; Coronary Artery Disease; Dietary Supplements; Disease Progression; Female; Folic Acid; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Selenium; Trace Elements; Ultrasonography, Interventional; Vitamin B 12; Vitamin B 6; Vitamin E; Vitamins

Low density lipoprotein (LDL) oxidative modification in the vascular wall seems to be a key factor in atherosclerosis development. Oxidised LDLs might recruit monocytes and favour their transformation into foam cells through a receptor-mediated intake (scavenger pathway). Moreover oxidised LDLs show cytotoxic potential which is probably responsible for endothelial cell damage and macrophage degeneration in the atherosclerotic human plaque. Following the oxidation hypothesis of atherosclerosis the role of natural antioxidants, i.e. Vitamin C, Vitamin E and carotenoids, has been investigated in a large number of epidemiological, clinical and experimental studies. Animal studies indicate that dietary antioxidants may reduce atherosclerosis progression, and observational data in humans suggest that antioxidant vitamin ingestion is associated with reduced cardiovascular disease, but the results of randomised controlled trials are mainly disappointing. It has been suggested that natural antioxidants may be effective only in selected subgroups of patients with high levels of oxidative stress or depletion of natural antioxidant defence systems. The favourable effects shown by some studies relating antioxidant dietary intake and cardiovascular disease, may have been exerted by other chemicals present in foods. Flavonoids are the ideal candidates, since they are plentiful in foods containing antioxidant vitamins (i.e. fruits and vegetables) and are potent antioxidants. Tea and wine, rich in flavonoids, seem to have beneficial effects on multiple mechanisms involved in atherosclerosis. Future studies should probably select patients in a context of high-oxidative stress / low-antioxidant defence, to verify if antioxidants may really prove useful as therapeutic anti-atherosclerotic agents.

Topics: Animals; Antioxidants; Ascorbic Acid; Atherosclerosis; Dietary Supplements; Flavonoids; Humans; Randomized Controlled Trials as Topic; Vitamin E; Vitamins

Topics: Arteriosclerosis; Ascorbic Acid; Atherosclerosis; Humans; Metabolism

The present study evaluated the risks and benefits of phytoestrogen treatment in healthy perimenopausal women in relation to the dynamics of climacteric syndrome and progression of atherosclerosis. Study participants were treated with placebo or phytoestrogen-rich natural preparation Karinat based on grape (Vitis vinifera) seeds, green tea (Camellia sinensis) leaves, hop (Hunulus lupulus) cone powder and garlic (Allium sativum) powder. The dynamics of climacteric syndrome was evaluated by Kupperman Index and Utian Quality of Life Scale. Atherosclerosis progression was evaluated by measuring carotid intima-media thickness. Significant changes of climacteric syndrome's severity in both Karinat and placebo groups (p = 0.005 and p = 0.001) were obtained after 24 months of follow-up. Detailed analysis of Kupperman Index suggested that Karinat possessed a significant effect on nervousness (p = 0.010), weakness (p = 0.020) and formication (p = 0.010). A significant improvement of medical (p = 0.070) and emotional (p = 0.060) components of Kupperman Index and Utian Quality of Life Scale was also observed in Karinat group. However, difference in carotid intima-media thickness between the two groups was not statistically significant at follow-up. A slight positive effect of phytoestrogens on climacteric syndrome manifestations was demonstrated in this study. Karinat can be used for alleviation of climacteric syndrome and cardiovascular disease prevention in perimenopausal women. Copyright © 2017 John Wiley & Sons, Ltd.

Topics: Adult; alpha-Tocopherol; Ascorbic Acid; Atherosclerosis; beta Carotene; Carotid Intima-Media Thickness; Double-Blind Method; Female; Humans; Middle Aged; Perimenopause; Phytoestrogens; Phytotherapy; Quality of Life

Regular consumption of fruit and vegetables may be associated with decreased CVD risk. In the present study, we investigated the effects of blackcurrant (BC) juice, rich in polyphenols and ascorbic acid, on oxidative and inflammatory biomarkers in cultured macrophages in vitro and in human subjects with an atherosclerosis-prone phenotype (after consumption of a high-energy meal). In cultured macrophages (RAW264.7), BC treatment significantly inhibited lipopolysaccharide-induced inflammation as indicated by lower mRNA levels of TNF-α, IL-1β and inducible NO synthase (iNOS) and lower nuclear p65 levels indicating decreased NF-κB activity. iNOS protein levels were lower and haem oxygenase 1 levels higher in BC-treated cells when compared with untreated controls. Subjects given a high-energy meal had elevated serum glucose and insulin levels with no significant difference between the BC-based juice and placebo treatment groups. TAG following meal ingestion tended to be attenuated after the BC treatment. Plasma ascorbic acid and radical-scavenging capacity were decreased following placebo meal consumption; however, BC significantly elevated both parameters compared with baseline and placebo ingestion. Plasma oxidised LDL, α-tocopherol and paraoxonase activity were unchanged in both treatment groups. Furthermore, production of TNF-α and IL-1β was not significantly changed by BC meal consumption. The present results suggest potential antioxidative and anti-inflammatory properties of BC in vitro in cultured macrophages. Although the observations were not directly transferable to a postprandial in vivo situation, the present results show that BC juice consumption may improve postprandial antioxidant status as indicated by higher ascorbic acid levels and free radical-scavenging capacity in plasma.

Topics: Adult; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Ascorbic Acid; Atherosclerosis; Beverages; Cell Line, Transformed; Cross-Over Studies; Diet, Atherogenic; Down-Regulation; Fruit; Humans; Hypertriglyceridemia; Inflammation Mediators; Macrophages; Male; Mice; Nitric Oxide Synthase Type II; Oxidative Stress; Postprandial Period; Ribes; Single-Blind Method

Vitamin E has been studied extensively in the prevention of atherosclerosis. Cross-sectional population studies as well as randomized controlled intervention trials have demonstrated conflicting results. A recent meta-analysis of these trials has emphasized the ineffectiveness of vitamin E in atherosclerosis prevention, with a possibility of harm at higher dosages. However, vitamin E has several isomers, with the alpha form being available via dietary supplements and the gamma form being available via dietary foodstuffs. The gamma form of vitamin E demonstrates several superior properties (such as trapping reactive nitrogen species and detoxifying nitrogen dioxide) compared with alpha vitamin E. All clinical trials have used the alpha isomer, with little concern that this isomer of vitamin E may actually suppress the gamma isomer of vitamin E. We undertook a dose-response study in volunteers with type 2 diabetes mellitus to include all the dosages of alpha vitamin E that have been used in cardiovascular prevention trials to determine the effect of alpha vitamin E on gamma vitamin E. We also assessed the effect of alpha vitamin E on several traditional markers of atherosclerotic risk. We added vitamin C to the vitamin E because several clinical trials included this vitamin to enhance the antioxidant effects of alpha vitamin E. Volunteers received, in randomized order for a 2-week period, one of the following vitamin dosage arms: (1) no vitamins, (2) low-dose supplemental vitamins E plus C, (3) medium-dose supplemental vitamins E plus C, and (4) high-dose supplemental vitamins E plus C. Blood levels of both alpha and gamma vitamin E were measured as well as surrogate markers of oxidative stress, hypercoagulation, and inflammation during a high-fat atherogenic meal (to increase the ambient oxidative stress level during the study). The results demonstrate that alpha vitamin E levels increased in proportion to the dose administered. However, at every dose of alpha vitamin E, gamma vitamin E concentration was significantly suppressed. No beneficial changes in surrogate markers of atherosclerosis were observed, consistent with the negative results of prospective clinical trials using alpha vitamin E. Our results suggest that all prospective cardiovascular clinical trials that used vitamin E supplementation actually suppressed the beneficial antioxidant gamma isomer of vitamin E. No beneficial effects on several potential cardiovascular risk factors were observed

Topics: Ascorbic Acid; Atherosclerosis; Cross-Over Studies; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Oxidative Stress; Risk Factors; Vitamin E

Essential hypertension is characterized by endothelial dysfunction, arterial stiffness, and increased oxidative stress. We evaluated the effect of short-term combined treatment with the antioxidants vitamins C and E on endothelial function, arterial stiffness, and oxidative stress in untreated essential hypertensive patients.. A randomized, double-blind, placebo-controlled, crossover study design was used to assign 30 male essential hypertensive patients to either vitamin C (1 g) and vitamin E (400 IU) or placebo for 8 weeks. Endothelium-dependent response was assessed as flow-mediated dilation (FMD) of the brachial artery. Arterial stiffness was assessed as central pulse wave velocity (PWV) and augmentation index (AIx). Plasma markers of oxidative stress and antioxidant status were measured.. After vitamin supplementation, FMD was significantly improved. Central PWV was significantly reduced, while AIx tended to decrease. Plasma vitamin levels and antioxidant capacity increased significantly. Levels of oxidative stress decreased. Changes in central PWV were related to changes in levels of oxidative stress.. Combined treatment with vitamins C and E has beneficial effects on endothelium-dependent vasodilation and arterial stiffness in untreated, essential hypertensive patients. This effect is associated with changes in plasma markers of oxidative stress.

Topics: Adult; Antioxidants; Ascorbic Acid; Atherosclerosis; Blood Pressure; Brachial Artery; Cross-Over Studies; Dietary Supplements; Double-Blind Method; Drug Therapy, Combination; Endothelium, Vascular; Humans; Hypertension; Male; Middle Aged; Oxidative Stress; Regional Blood Flow; Vasodilation; Vitamin E

The aim of the study was to analyze the lipid and lipoprotein oxidation profile in patients with end stage renal disease who started haemodialysis and also to evaluate the possible effect of haemodialysis and vitamin C supplementation on lipoprotein oxidation one year after the initiation of the therapy.. Forty-one end stage renal disease patients who started haemodialysis between January 1999 and January 2000 were enrolled in the study. The patients were randomised to receive 1,000 mg/day of vitamin C or placebo and then hemodialysis was initiated. We measured the lipid profile and the susceptibility of LDL and HDL to oxidation using cooper ions, at the moment of inclusion and one-year after the treatment.. No significant differences were observed among the vitamin-C treated patients and those who received placebo. Our results show that haemodialysis by itself did not induce deletereous effects on the lipid profile, which was slightly improved. A small decrease in total cholesterol--183 to 164 mg/dl (group A), 170 to 144 mg/dl (group B); in LDL cholesterol (100 mg/dl to 79 mg/dl (group A), 88 mg/dl to 73 mg/dl (Group B); and in phospholipids [198 to 188 mg/dl, group A (Group A), 195 mg/dl to 178 mg/dl (Group B)], was observed in all the patients one year after starting haemodialysis. When considering oxidation-derivative products, the lag phase of LDL-cholesterol and HDL-cholesterol was enlarged but without statistical significance. A tendency to increase the vitamin E generation in HDL and LDL lipoproteins was observed in vitamin-C treated patients, but the difference still remained not significant.. Haemodialysis by itself could improve lipid profile in patients with a previous pro-oxidative state such as uraemia. Although our results have failed to demonstrate significant differences between vitamin C-treated and not treated patients, the tendency to decrease oxidation products by supplementation of vitamin C could mean a beneficial effect on oxidation parameters. In order to improve oxidative stress, the use of lipophylic more than hydrophilic vitamins could be evaluated in randomized studies with a more important number of patients.

Topics: Ascorbic Acid; Atherosclerosis; Female; Humans; Kidney Failure, Chronic; Lipid Peroxidation; Lipoproteins; Male; Middle Aged; Renal Dialysis; Vitamins

Ascorbic acid and calcitriol were frequently utilized in conjunction as therapy during the COVID-19 pandemic, and individuals with minor symptoms had notable improvements. There have been a few studies, often with conflicting findings, that examine the use of them for endothelium restoration and numerous clinical trial studies that failed to establish the efficacy. The aim of this study was to find the efficacy of ascorbic acid compared to calcitriol on the inflammatory markers monocyte chemoattractant protein-1 (MCP-1), nitric oxide (NO), and superoxide dismutase (SOD), as protective agents which play an important role in the early stages of atherosclerosis formation. This study was an experimental in vivo study.. Ascorbic acid and calcitriol treatment was significantly effective (. Both treatments could reduce MCP-1, and increase NO and SOD by increasing antioxidants. In this study calcitriol was superior to ascorbic acid in increasing SOD, but not NO and decreasing MCP-1. According to the theory, it was found that calcitriol through nuclear factor erythroid 2-related factor 2 (Nrf2) causes a direct increase in the amount of SOD. Nrf2 is an emerging regulator of cellular resistance to oxidants.. Ascorbic acid and calcitriol treatment was able to reduce MCP-1 and increase NO and SOD in atherosclerosis rat. Calcitriol was significantly superior in increasing SOD levels compared to ascorbic acid.

Topics: Animals; Ascorbic Acid; Atherosclerosis; Calcitriol; Chemokine CCL2; Male; NF-E2-Related Factor 2; Nitric Oxide; Oxidative Stress; Rats; Rats, Wistar; Superoxide Dismutase

The current paper deals with the development of a new biologically active food supplement (BAFS) aimed at treating atherosclerosis. Since atherosclerosis is considered to be a disease of aging, the composition of the supplement includes such essential minerals as magnesium and potassium, which are commonly used to prevent atherosclerosis, as well as vitamins C, E and the B-group vitamins in order to address the needs of the elderly. The authors outline the supplement-manufacturing technology and discuss the clinical trial undertaken by patients, aged about 60 years, with peripheral atherosclerosis. The research methodology focuses on studying the effectiveness of the developed supplement by assessing the influence of the active ingredients on treating metabolic disorders. To establish the efficacy of the supplement, blood tests, ultrasound and physical examinations were applied. The combination therapy resulted in improved metabolism and an overall better performance of the cardiovascular system; therefore, the BASF can be recommended as part of combination therapy to prevent and treat atherosclerotic and age-related changes in blood vessels.

Topics: Aged; Ascorbic Acid; Atherosclerosis; Clinical Trials as Topic; Dietary Supplements; Humans; Minerals; Vitamins

Atherosclerosis is an important medical problem of modern society. High environmental tobacco smoke in casino is associated with an accelerated atherogenic process. We have previously shown vitamin B12 and C supplementation improves vascular reactivity and may be beneficial in vascular protection.. To evaluate the impact of vitamin supplementation on atherosclerosis (brachial artery reactivity FMD and carotid intima-media thickness IMT) in subjects exposed to high environmental tobacco smoke.. Double-blind 2x2 factorial design fashion.. Computer randomization in 4 treatment groups: placebo (n=24), vitamin B12 (n=21), vitamin C (n=23) and vitamin B12+C (n=23) groups.. 91 passive-smoking casino employees (19.2% male, mean age 45.0±8.2 years).. Subjects were randomized to receive vitamin B12 (500µg daily), vitamin C (200mg daily), vitamin B12+C or image-matched placebo capsules for 1 year.. Brachial FMD and carotid IMT (surrogate atherosclerotic markers) were measured by ultrasound at baseline and on completion at 12 months.. 91 passive smoking casino employees (19.2% male, mean age 45.0±8.2 years) were randomized to receive vitamin B12 (500µg daily), vitamin C (200mg daily), vitamin B12+C or image-matched placebo capsules in double-blind 2 x 2 factorial design fashion for 1 year. Brachial FMD and carotid IMT (surrogate atherosclerotic markers) were measured by ultrasound at baseline and 12 months.. Of the 78 (85.7%) passive-smoking employees completed the study, 11.5% had hypertension, 5.1% diabetes mellitus and 15.4% hypercholesterolemia. There were no significant changes in their blood pressures, lipid profiles, glucose and body mass index after supplementation for 1 year, but mild decrease in DBP (p<0.001) and blood creatinine (p<0.01) after combined vitamin B12 and C, and significant increase in blood B12 after vitamin B12 (p<0.01) and vitamin B12+C supplementations (p<0.001). Brachial FMD and cartotid IMT improved after the 3 vitamin supplementations (p<0.001), but not after placebo, being more significant after combined vitamin supplementations (p<0.0001). No adverse effects were reported.. Vitamin B12 or C supplementation in passive smokers improved vascular reactivity and structures at 1 year, with implication in long term atherosclerosis prevention.

Topics: Ascorbic Acid; Atherosclerosis; Carotid Arteries; Dietary Supplements; Double-Blind Method; Female; Humans; Male; Middle Aged; Smokers; Smoking; Vitamin B 12

(1) Background: Tissue non-specific alkaline phosphatase (TNAP) is suspected to induce atherosclerosis plaque calcification. TNAP, during physiological mineralization, hydrolyzes the mineralization inhibitor inorganic pyrophosphate (PP

Topics: Adenosine Triphosphate; Alkaline Phosphatase; Animals; Aorta; Ascorbic Acid; Atherosclerosis; Cell Transdifferentiation; Chondrocytes; Diphosphates; Glycerophosphates; Humans; Magnetic Resonance Spectroscopy; Mice; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Phosphates; Vascular Calcification

Atherosclerosis is a major contributor to cardiovascular disease, with a higher burden on men than women during the occupational age. Intake of individual dietary antioxidants is inversely associated with risk of atherosclerosis development. We aimed to understand the relationship between dietary composite antioxidant intake and the carotid intima media thickness (cIMT), which is a proxy of atherosclerosis progression.. We performed a cross-sectional analysis that included 894 members of the Kardiovize cohort, a random urban sample population. Nutrient intakes were derived by 24-h recall. We constructed a composite dietary antioxidant index (CDAI), based on zinc, selenium, vitamin A, vitamin C, vitamin E and carotenoids. We considered the CDAI as the exposure variable and primary outcomes were the following cardio-metabolic parameters: body mass index (BMI), waist-to-hip ratio (WHR), body fat mass (BFM), systolic and diastolic blood pressure, triglycerides, HDL and LDL cholesterol, and cIMT. Associations and interactions between variables were evaluated using linear regression analyses. In women, a 1 mg increase in dietary intake of zinc or vitamin E decreased the cIMT by 3.36 and 1.48 µm, respectively, after adjusting for covariates. Similarly, the cIMT decreased by 4.72 µm for each one-unit increase in CDAI (p = 0.018). Beyond CDAI, age (β = 3.61; SE=0.89; p = 0.001), systolic blood pressure (β = 1.30; SE=0.59; p = 0.029) and triglycerides (β = 22.94; SE=10.09; p = 0.024) were significant predictors of cIMT in women. By contrast, we found no association between CDAI and cIMT in men.. CDAI negatively associates with cIMT in women. These findings indicate that combined intake of nutrients with anti-oxidant properties might prevent the initiation and progression of arterial lesions in a sex-specific manner.

Topics: Adipose Tissue; Adult; Antioxidants; Ascorbic Acid; Atherosclerosis; Body Mass Index; Carotenoids; Carotid Intima-Media Thickness; Cholesterol, HDL; Cholesterol, LDL; Cross-Sectional Studies; Dietary Supplements; Disease Progression; Female; Humans; Male; Middle Aged; Selenium; Sex Factors; Triglycerides; Vitamin A; Vitamin E; Waist-Hip Ratio; Zinc

The oxidative process in atherogenesis generated by proinflammatory induction and response to antioxidants vitamins in an experimental model were analyzed.. Male rats were used: (A)Control, (B)Control+vitamin E plus C, (C)Hyperfibrinogenemia and (D)Hyperfibrinogenemia+vitamins E plus C. Hyperfibrinogenemia induced by daily injection of adrenaline (0.1mg/day/rat) for 120 days.. 3.42 mg/kg of vitamin E plus 2.14 mg/kg of vitamin C, fifteen days after induction. Vascular histology analyzed by optical microscopy. Fibrinogen, nitrites and superoxide dismutase analyzed by spectrophotometry.. MANOVA, Hotelling test for post testing, significance level p<0.05.. (C) group showed higher fibrinogen than (A) and (B)(p<0.001). Compared to (C) group, (D) showed a decrease of fibrinogen (p<0.001). A marked increase in nitrites was found in (C) versus (A), (B) and (D) groups (p<0.001). Superoxide dismutase activity increased in (C) group compared to groups (A) and (B) (p<0.001). In the group (D) an increase of the activity of this enzyme was observed in comparison to groups (C)(p<0.001), (A) and (B) (p<0.0001 in both). The (C) group shown endothelial denudation, thickening of the vascular intima and extracellular matrix enlargement with foam cells(p<0.001).. These results strongly suggest that vitamins E plus C produce regression of inflammatory and oxidative stress processes in this experimental model.

Topics: alpha-Tocopherol; Animals; Antioxidants; Aorta, Thoracic; Ascorbic Acid; Atherosclerosis; Biomarkers; Endothelium, Vascular; Fibrinogen; Male; Nitric Oxide; Oxidative Stress; Rats, Wistar; Superoxide Dismutase

High-fat diet (HFD) is known to cause endothelial dysfunction and contribute to atherosclerosis progression. The objective of this study was to evaluate the efficacy of L-arginine (L-Arg) and vitamin C supplementation as a potentially useful strategy for modulation of serum homocysteine (Hcy) levels, tumor necrosis factor alpha (TNF-α), oxidative stress, and insulin resistance induced by HFD in rats. Six weeks-old female and male Wistar rats were divided into five groups of twelve rats each and treated for six weeks with: group 1, standard diet; group 2, HFD; group 3, HFD supplemented with L-Arg (20g/kg diet); group 4, HFD supplemented with L-Arg (20g/kg diet) plus vitamin C (100mg/kg diet); group 5, HFD supplemented with vitamin C (100mg/kg diet). HFD significantly elevated TNF-α, reduced total antioxidant status (TAS), and increased insulin resistance (HOMA-IR). Significant increases of total cholesterol (TCH), LDL cholesterol (LDL), triglyceride (TG) and a decrease of HDL cholesterol (HDL) were observed in HFD rats. Supplementation with l-Arg prevented the decrease of TAS and the increases in HOMA-IR, LDL, and TG levels. Moreover, Hcy and TNF-α levels were reduced in L-Arg supplemented group. Supplementation with vitamin C significantly atenuated TAS decrease and lowered LDL levels. L-Arg plus vitamin C enhanced L-Arg effect on TAS and protected against TNF-α increase. Western blot analysis showed that l-Arg supplementation of HFD rats reduced the level of protein carbonyls. Taken together, these findings indicate that supplemental l-arginine and/or vitamin C, by their abilities to modulate biomarkers of HFD-induced endothelial dysfunction, are anti-atherogenic.

Topics: Animals; Antioxidants; Arginine; Ascorbic Acid; Atherosclerosis; Biomarkers; Diet, High-Fat; Dietary Supplements; Endothelium, Vascular; Female; Insulin Resistance; Lipids; Male; Oxidative Stress; Rats; Rats, Wistar

Oxidative modification of low-density lipoprotein (LDL) appears to be an early step in the pathogenesis of atherosclerosis. Meanwhile, myeloperoxidase (MPO)-catalyzed reaction is one of the potent pathway for LDL oxidation in vivo. The aim of this study was to evaluate in vitro antioxidant effects of vitamins C and E on LDL oxidation mediated by MPO.. MPO was isolated from fresh plasma by sequential centrifugation using density ultracentrifugation. It was incubated with LDL and the LDL oxidation level was determined spectrophotometrically by measuring conjugated diene absorbance at 234 nm. Furthermore, vitamin C (50-200 mM) and vitamin E (10-40 mM) were added and the LDL oxidation level was determined.. The purity index of MPO and its enzymatic activity were 0.69 and 1127 U/mg protein, respectively. It was demonstrated that vitamin C in vitro inhibited LDL oxidation mediated by MPO; however, vitamin E was unable to act in the same way. The protection by vitamin C was concentration dependent and maximum protective effect of vitamin C was observed at 150 mM, where about 64% of the LDL oxidation was inhibited. Vitamin C increased lag time of LDL oxidation mediated by MPO up to 2.4 times.. It can be concluded from our results that vitamin C is able to improve LDL resistance to oxidative modification in vitro. In addition, vitamin C might be effective in LDL oxidation mediated by MPO in vivo, resulting in reduction of atherosclerosis process rate.

Topics: Antioxidants; Ascorbic Acid; Atherosclerosis; Humans; Lipid Peroxidation; Lipoproteins, LDL; Oxidation-Reduction; Peroxidase; Vitamin E

To test whether severe ascorbic acid deficiency in macrophages affects progression of early atherosclerosis, we used fetal liver cell transplantation to generate atherosclerosis-prone apolipoprotein E-deficient (apoE(-/-)) mice that selectively lacked the ascorbate transporter (SVCT2) in hematopoietic cells, including macrophages. After 13 weeks of chow diet, apoE(-/-) mice lacking the SVCT2 in macrophages had surprisingly less aortic atherosclerosis, decreased lesion macrophage numbers, and increased macrophage apoptosis compared to control-transplanted mice. Serum lipid levels were similar in both groups. Peritoneal macrophages lacking the SVCT2 had undetectable ascorbate; increased susceptibility to H(2)O(2)-induced mitochondrial dysfunction and apoptosis; decreased expression of genes for COX-2, IL1β, and IL6; and decreased lipopolysaccharide-stimulated NF-κB and antiapoptotic gene expression. These changes were associated with decreased expression of both the receptor for advanced glycation end products and HIF-1α, either or both of which could have been the proximal cause of decreased macrophage activation and apoptosis in ascorbate-deficient macrophages.

Topics: Animals; Apolipoproteins E; Ascorbic Acid; Ascorbic Acid Deficiency; Atherosclerosis; Cells, Cultured; Disease Progression; Female; Genetic Predisposition to Disease; Macrophages, Peritoneal; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Organ Specificity; Organic Anion Transporters, Sodium-Dependent; Sodium-Coupled Vitamin C Transporters; Symporters; Time Factors

Endothelial dysfunction has recently been demonstrated in obstructive sleep apnea (OSA), but the underlying mechanisms are not entirely understood. Oxidative stress is a typical feature of OSA.. We investigated the influence of oxidative stress and continuous positive airway pressure (CPAP) on microvascular endothelial function in OSA.. Endothelial function of forearm resistance vessels was assessed by strain gauge venous occlusion plethysmography after intra-arterial infusion of the endothelium-independent vasodilator sodium nitroprusside (1.6, 3.2, and 4.0 μg/min) and the endothelium-dependent vasodilator acetylcholine (Ach, 15, 30 and 40 μg/min) in patients with (n = 11) and without (n = 8) OSA (apnea-hypopnea index ≥15/h). These measurements have been repeated after local intra-arterial infusion of the antioxidant vitamin C (25 μg/min). Furthermore, 6 patients have been reevaluated after 6 months of OSA treatment.. Patients with OSA demonstrated impaired endothelial function compared to those without OSA. Thus, related to baseline flow, the increase in forearm blood flow induced by Ach was blunted in patients with OSA (148.7 ± 29.7% in OSA vs. 233.6 ± 45.7% in controls, p = 0.001). This difference, however, was abolished by co-infusion of vitamin C. Endothelial function markedly improved following treatment in 5 of 6 OSA patients.. This study strongly suggests that microvascular endothelial function is affected by OSA predominantly through increased oxidative stress, and treatment of OSA may improve endothelial function mainly by reducing oxidative stress. The role of oxidative stress-induced endothelial dysfunction as a potential promoter of atherosclerosis and an increased cardiovascular risk in patients with OSA should be investigated in further controlled studies.

Topics: Acetylcholine; Ascorbic Acid; Atherosclerosis; Blood Flow Velocity; Capillaries; Continuous Positive Airway Pressure; Endothelium, Vascular; Female; Forearm; Humans; Infusions, Intra-Arterial; Male; Microcirculation; Middle Aged; Nitroprusside; Oxidative Stress; Plethysmography; Polysomnography; Prospective Studies; Sleep Apnea, Obstructive; Vascular Resistance; Vasodilator Agents

Chronic inflammation and proatherogenic lipids are important risk factors of cardiovascular disease (CVD). Specific dietary constituents such as polyphenols and fish oils may improve cardiovascular risk factors and may have a beneficial effect on disease outcomes. We hypothesized that the intake of an antiinflammatory dietary mixture (AIDM) containing resveratrol, lycopene, catechin, vitamins E and C, and fish oil would reduce inflammatory risk factors, proatherogenic lipids, and endpoint atherosclerosis. AIDM was evaluated in an inflammation model, male human C-reactive protein (CRP) transgenic mice, and an atherosclerosis model, female ApoE*3Leiden transgenic mice. Two groups of male human-CRP transgenic mice were fed AIDM [0.567% (wt:wt) powder and 0.933% (wt:wt oil)] or placebo for 6 wk. The effects of AIDM on basal and IL-1β-stimulated CRP expression were investigated. AIDM reduced cytokine-induced human CRP and fibrinogen expression in human-CRP transgenic mice. In the atherosclerosis study, 2 groups of female ApoE*3Leiden transgenic mice were fed an atherogenic diet supplemented with AIDM [0.567% (wt:wt) powder and 0.933% (wt:wt oil)] or placebo for 16 wk. AIDM strongly reduced plasma cholesterol, TG, and serum amyloid A concentrations compared with placebo. Importantly, long-term treatment of ApoE*3Leiden mice with AIDM markedly reduced the development of atherosclerosis by 96% compared with placebo. The effect on atherosclerosis was paralleled by a reduced expression of the vascular inflammation markers and adhesion molecules inter-cellular adhesion molecule-1 and E-selectin. Dietary supplementation of AIDM improves lipid and inflammatory risk factors of CVD and strongly reduces atherosclerotic lesion development in female transgenic mice.

Topics: Acute-Phase Proteins; Animals; Antioxidants; Apolipoprotein E3; Ascorbic Acid; Atherosclerosis; Biomarkers; C-Reactive Protein; Carotenoids; Catechin; Diet; Female; Fish Oils; Humans; Lycopene; Male; Mice; Mice, Transgenic; Resveratrol; Risk Factors; Stilbenes; Vitamin E

It is well known that extracts of purple sweet potato (PSP) have potent antioxidant activity. However, it has not been established whether extracts of PSP inhibit oxidation of low-density lipoprotein (LDL) or protein glycation. LDL oxidation and protein glycation are well-known risk factors for chronic metabolic diseases, such as atherosclerosis and diabetes mellitus. Chopped and sliced PSP and yellow sweet potato (YSP) were extracted individually at a concentration of 1 g of PSP tuber/mL using either ethanol or water for 6 hours. The PSP ethanol extract (100-fold diluted) showed stronger radical (2,2-diphenyl-1-picrylhydrazyl radical) scavenging activity than the water extract of PSP and the ethanol extract of YSP (up to a sixfold higher activity). The ethanol extract of PSP also exhibited the highest increase in ferric reducing ability among all extracts. Cupric ion-mediated LDL oxidation was strongly inhibited by the ethanol extract of PSP, with similar potency to vitamin C treatment (final concentration, 10 mM). The PSP extract strongly inhibited fructose-mediated protein glycation as determined by fluorescence spectroscopy. The PSP extract-treated apolipoprotein (apo) A-I showed a decreased multimerization pattern on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, whereas glycated apoA-I showed the strongest multimeric band. PSP extract treatment also inhibited the uptake of oxidized LDL into human macrophage cells with suppression of malondialdehyde production in the cell culture medium. In conclusion, these results suggest that the extract of PSP can be used as a putative anti-atherosclerotic and antidiabetic agent with strong antioxidant functions. This is the first report to show the biological functions of PSP extract to treat hyperlipidemic and hyperglycemic disorders.

Topics: Antioxidants; Apolipoprotein A-I; Ascorbic Acid; Atherosclerosis; Biphenyl Compounds; Cholesterol, LDL; Fructose; Glycation End Products, Advanced; Glycosylation; Humans; Ipomoea batatas; Lipid Peroxidation; Macrophages; Malondialdehyde; Phytotherapy; Picrates; Plant Extracts; Plant Roots

Previous studies have shown that the increase of carbamylated LDL (cLDL), a product of nonenzymatic modification of LDL in human serum by urea-derived cyanate, may cause cardiovascular complications in patients with chronic renal insufficiency. This study examined the inhibitory effect of ascorbic acid, alpha-tocopherol and lycopene on LDL carbamylation in an in vitro model system.. After isolation of LDL from plasma using an ultracentrifuge technique, cyanate was added to it and then LDL carbamylation was measured in both the absence and presence of ascorbic acid, alpha-tocopherol and/or lycopene by the colorimetric method at 530 nm.. The findings indicated that these vitamins inhibit LDL carbamylation and the most effective vitamin of the three is lycopene. Moreover, the effect of lycopene on this process increased in the presence of ascorbic acid and alpha-tocopherol.. This study indicated that ascorbic acid, alpha-tocopherol and lycopene with antioxidant activity can probably inhibit LDL carbamylation and therefore may have a role in ameliorating atherosclerotic risk of patients with kidney failure. However in vitro and in vivo investigations are required to confirm the exact effects of these vitamins on patients suffering from uremic disorders.

Topics: Adult; alpha-Tocopherol; Ascorbic Acid; Atherosclerosis; Carotenoids; Citrulline; Cyanates; Electrophoresis, Agar Gel; Humans; Lipoproteins, LDL; Lycopene; Male; Protein Processing, Post-Translational; Uremia; Vitamins; Young Adult

Cigarette smoking is a major risk for developing atherosclerosis; however, the underlying mechanism is poorly understood. This paucity of knowledge is largely attributed to the lack of an animal model; therefore, our efforts were targeted towards establishing cigarette smoke (CS)-induced atherosclerosis in guinea pig. To understand the mechanism, we investigated apoptosis, an event implicated in atherosclerosis, in the aorta of CS-exposed animals. Since a major deleterious effect of CS is oxidative stress, we also examined the effect of vitamin C, an antioxidant, on CS- induced atherosclerosis.. Guinea pigs on a diet with or without vitamin C supplement were exposed to CS for different time periods. Aortal sections from these animals were examined for atherosclerotic changes by staining with H&E and Oil red O. Atherogenic changes were observed in sections obtained from CS-exposed guinea pigs only. TUNEL assay showed the occurrence of apoptosis in CS-exposed guinea pig aorta. Our results revealed that CS-induced apoptosis could contribute to the progression but not to the initiation of the disease. Immunohistochemical analysis documents that CS-induced apoptosis in aortal sections is mediated at least in part by an increased Bax/Bcl2 ratio. In contrast, CS-exposed guinea pigs fed with vitamin C-supplemented diet exhibit little or no atherogenic changes. This anti-atherosclerotic activity of vitamin C can be attributed partly to its ability to inhibit CS-induced apoptosis and platelet activation.. Exposure of guinea pigs to cigarette smoke causes the development of atherosclerosis, which can be prevented by vitamin C supplement.

Topics: Animals; Antioxidants; Aorta; Apoptosis; Ascorbic Acid; Atherosclerosis; Dietary Supplements; Disease Models, Animal; Guinea Pigs; Immunoenzyme Techniques; In Situ Nick-End Labeling; Male; Oxidative Stress; Platelet Activation; Smoking

To assess the role of combined deficiencies of vitamins C and E on the earliest stages of atherosclerosis (an inflammatory condition associated with oxidative stress), 4 combinations of vitamin supplementation (low C/low E, low C/high E, high C/low E, and high C/high E) were studied in atherosclerosis-prone apolipoprotein E-deficient mice also unable to synthesize their own vitamin C (gulonolactone oxidase(-/-)); and to evaluate the effect of a more severe depletion of vitamin C alone in a second experiment using gulonolactone oxidase(-/-) mice carrying the hemizygous deletion of SVCT2 (the vitamin C transporter).. After 8 weeks of a high-fat diet (16% lard and 0.2% cholesterol), atherosclerosis developed in the aortic sinus areas of mice in all diet groups. Each vitamin-deficient diet significantly decreased liver and brain contents of the corresponding vitamin. Combined deficiency of both vitamins increased lipid peroxidation, doubled plaque size, and increased plaque macrophage content by 2- to 3-fold in male mice, although only plaque macrophage content was increased in female mice. A more severe deficiency of vitamin C in gulonolactone oxidase(-/-) mice with defective cellular uptake of vitamin C increased both oxidative stress and atherosclerosis in apolipoprotein E(-/-) mice compared with littermates receiving a diet replete in vitamin C, again most clearly in males.. Combined deficiencies of vitamins E and C are required to worsen early atherosclerosis in an apolipoprotein E-deficient mouse model. However, a more severe cellular deficiency of vitamin C alone promotes atherosclerosis when vitamin E is replete.

Topics: Animals; Aortic Diseases; Apolipoproteins E; Ascorbic Acid; Ascorbic Acid Deficiency; Atherosclerosis; Brain; Dietary Supplements; Disease Models, Animal; Disease Progression; Female; L-Gulonolactone Oxidase; Lipid Peroxidation; Liver; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardium; Organic Anion Transporters, Sodium-Dependent; Oxidative Stress; Severity of Illness Index; Sex Factors; Sodium-Coupled Vitamin C Transporters; Symporters; Time Factors; Vitamin E; Vitamin E Deficiency; Vitamins

Although hemodialysis (HD) is essential for end-stage renal disease patients, at the same time it causes oxidative stress and long-term pro-atherosclerotic effects. This study aimed to determine lipid profile as well as the total antioxidant capacity (TAC) and vitamins A, E, and C in HD patients. The study enrolled 31 patients (50.3 ± 14.9 years old) undergoing maintenance 4-hour HD three times per week with a polysulfone membrane dialyzer for a mean of 76.1 months (range, 7-120 months) and 31 healthy individuals (47.8 ± 13.9 years old). Lipid profiles were determined spectrophotometrically using commercially available kits. Total antioxidant capacity was determined by ferric reducing/antioxidant power assay, levels of vitamins A and E were assayed using high-pressure liquid chromatography, and the level of vitamin C was measured by a photometric method. Our results showed that before HD, the levels of TAC and vitamin A were significantly higher than in normal subjects, whereas the levels of high-density lipoprotein (HDL) and vitamin C were lower than in control subjects (P < .001). There was no significant difference between normal subjects and patients before dialysis regarding low-density lipoprotein (LDL) and vitamin E levels (P > .05). After HD, the levels of HDL-cholesterol, vitamins E and C, and TAC decreased significantly (P < .001), but the decreased level of vitamin A still remained higher than controls (P < .05), whereas the levels of LDL were significantly higher than controls (P < .001). In conclusion, alterations in the lipoprotein profiles and antioxidant markers following HD suggest an increased risk of atherosclerosis in these patients.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Atherosclerosis; Female; Humans; Kidney Failure, Chronic; Lipids; Lipoproteins, HDL; Lipoproteins, LDL; Male; Middle Aged; Oxidative Stress; Renal Dialysis; Reproducibility of Results; Vitamin A; Vitamin E

Low intake of nutrients is associated with poor health outcomes. We examined the contribution of dietary supplementation to meeting recommended dietary intakes of calcium, magnesium, potassium, and vitamin C in participants of the Multi-Ethnic Study of Atherosclerosis, a cohort of white, African-American, Hispanic, and Chinese-American participants ages 45 to 84 years. We also assessed the prevalence of intakes above Tolerable Upper Intake Levels (ULs).. At the baseline exam in 2000-2001, 2,938 men and 3,299 women completed food frequency questionnaires and provided information about dietary supplementation. We used relative risk regression to estimate the probability of meeting Recommended Dietary Allowances (RDAs) or Adequate Intakes (AIs) in supplement users vs nonusers and Fisher's exact tests to compare the proportion of those exceeding ULs between the two groups. RDAs, AIs, and ULs were defined by the National Academy of Sciences Food and Nutrition Board's Dietary Reference Intakes (DRIs).. After adjustment for age and education, the relative risk of meeting RDAs or AIs in supplement-users vs nonusers ranged from 1.9 (1.6, 2.3) in white men to 5.7 (4.1, 8.0) in African-American women for calcium, from 2.5 (1.9, 3.3) in Hispanic men to 5.2 (2.4, 11.2) in Chinese men for magnesium, and from 1.4 (1.3, 1.5) in African-American women to 2.0 (1.7, 2.2) in Chinese men for vitamin C. The relative risks for meeting RDAs for calcium differed significantly by ethnicity (P<0.001) and sex (P<0.001), and by ethnicity for magnesium (P=0.01). The relative risk for each sex/ethnicity strata was close to 1 and did not reach statistical significance at alpha=.05 for potassium. For calcium, 15% of high-dose supplement users exceeded the UL compared with only 2.1% of nonusers. For vitamin C, the percentages were 6.6% and 0%, and for magnesium, 35.3% and 0% (P<0.001 for all).. Although supplement use is associated with meeting DRI guidelines for calcium, vitamin C and magnesium, many adults are not meeting the DRI guidelines even with the help of dietary supplements, and the effect of supplementation can vary according to ethnicity and sex. However, supplementation was not significantly associated with meeting DRIs for potassium. Also, high-dose supplement use is associated with intakes above ULs for calcium, magnesium, and vitamin C.

Topics: Aged; Aged, 80 and over; Aging; Ascorbic Acid; Asian; Atherosclerosis; Black or African American; Calcium, Dietary; Cohort Studies; Diet Surveys; Dietary Supplements; Ethnicity; Female; Hispanic or Latino; Humans; Magnesium; Male; Middle Aged; Nutrition Policy; Nutritional Physiological Phenomena; Nutritional Requirements; Potassium, Dietary; Risk Factors; Sex Factors; Statistics, Nonparametric; Surveys and Questionnaires; White People

Periodontitis has been causally linked to cardiovascular disease, which is mediated through the oxidative stress induced by periodontitis. Since vitamin C has been suggested to limit oxidative damage, we hypothesized that vitamin C intake may reduce endothelial oxidative stress induced by periodontitis in the aorta. The aim of this study was to investigate the effects of vitamin C intake on the initiation of atherosclerosis in a ligature-induced rat periodontitis model.. Eighteen 8-week-old-male Wistar rats were divided into three groups of six rats and all rats received daily fresh water and powdered food through out the 6-week study. In the vitamin C and periodontitis groups, periodontitis was ligature-induced for the first 4 weeks. In the vitamin C group, rats were given distilled water containing 1 g/L vitamin C for the 2 weeks after removing the ligature.. In the periodontitis group, there was lipid deposition in the descending aorta and significant increases of serum level of hexanoyl-lysine (HEL), and aortic levels of nitrotyrosine expression, HEL expression and 8-hydroxydeoxyguanosine (8-OHdG) compared to the control group. Vitamin C intake significantly increased plasma vitamin C level and GSH:GSSG ratio (178% and 123%, respectively), and decreased level of serum HEL and aortic levels of nitrotyrosine, HEL and 8-OHdG (23%, 87%, 84%, and 38%, respectively).. These results suggest that vitamin C intake attenuates the degree of experimental atherosclerosis induced by periodontitis in the rat by decreasing oxidative stress.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antioxidants; Aorta, Thoracic; Aortic Diseases; Ascorbic Acid; Atherosclerosis; Deoxyguanosine; Endothelium, Vascular; Glutathione; Lysine; Male; Oxidative Stress; Periodontitis; Random Allocation; Rats; Rats, Wistar; Tyrosine; Vitamins

Hitherto unknown efficacy of the peel extracts of Mangifera indica (MI), Cucumis melo (CM) and Citrullus vulgaris (CV) fruits in ameliorating the diet-induced alterations in dyslipidemia, thyroid dysfunction and diabetes mellitus have been investigated in rats. In one study, out of 4 different doses (50-300 mg/kg), 200 mg/kg of MI and 100 mg/kg for other two peel extracts could inhibit lipidperoxidation (LPO) maximally in liver. In the second experiment rats were maintained on pre-standardized atherogenic diet CCT (supplemented with 4% cholesterol, 1% cholic acid and 0.5% 2-thiouracil) to induce dyslipidemia, hypothyroidism and diabetes mellitus and the effects of the test peel extracts (200 mg/kg of MI and 100 mg/kg for CM and CV for 10 consecutive days) were studied by examining the changes in tissue LPO (in heart, liver and kidney), concentrations of serum lipids, thyroid hormones, insulin and glucose. Rats, treated simultaneously with either of the peel extracts reversed the CCT-diet induced increase in the levels of tissue LPO, serum lipids, glucose, creatinine kinase-MB and decrease in the levels of thyroid hormones and insulin indicating their potential to ameliorate the diet induced alterations in serum lipids, thyroid dysfunctions and hyperglycemia/diabetes mellitus. A phytochemical analysis indicated the presence of a high amount of polyphenols and ascorbic acid in the test peel extracts suggesting that the beneficial effects could be the result of the rich content of polyphenols and ascorbic acid in the studied peels.

Topics: Animals; Ascorbic Acid; Atherosclerosis; Blood Glucose; Citrullus; Creatine Kinase, MB Form; Cucumis melo; Diabetes Mellitus; Diet, Atherogenic; Dyslipidemias; Flavonoids; Fruit; Hyperglycemia; Hypoglycemic Agents; Hypothyroidism; Lipid Peroxidation; Lipids; Mangifera; Phenols; Phytotherapy; Plant Extracts; Polyphenols; Rats; Rats, Wistar; Thyroxine; Triiodothyronine

Oxalic acid (OA) is thought to be a uremic toxin that participates in the pathogenesis of uremic syndrome. The objectives of this study were to: (1) evaluate the plasma levels of OA in patients with chronic renal disease with various levels of glomerular filtration rate and after renal transplantation; (2) investigate the salivary secretion of OA and ascorbic acid in healthy subjects and in patients with chronic renal failure (CRF); (3) examine the influence of water and sodium diuresis and furosemide administration on the urinary excretion of OA and ascorbic acid in healthy subjects and in CRF patients without dialysis treatment; and (4) evaluate the influence of renal replacement therapy (RRT) on secondary hyperoxalemia in hemodialysis patients.. This study was conducted at the Nephrological Department of P.J. Safárik University. Sixty-one patients with chronic renal disease, 64 CRF patients, 32 continuous ambulatory peritoneal dialysis (CAPD) patients, 15 hemodialysis patients, 21 patients after renal transplantation, and 15 healthy subjects were examined. Maximal water diuresis, diets with low (2 g/day) and high (15 g/day) sodium intake, administration of intravenous furosemide (20 mg), and renal replacement therapy (CAPD, hemodialysis, hemofiltration, and postdilution hemodiafiltration) were utilized in the study.. In patients with chronic renal disease and those after renal transplantation, direct relationships between plasma OA and serum creatinine were found (r = 0.904 and 0.9431, respectively, P < .01). Despite a high level of plasma OA in uremic patients (23.1 +/- 10 micromol/L), there was no significant difference in salivary OA between control subjects (128 +/- 19 micromol/L) and CRF patients (135 +/- 24 micromol/L). The urinary excretion of OA during maximal water diuresis (from 37.5 to 110.3 micromol/4 hours) and after intravenous furosemide (from 34.5 to 66.7 micromol/3 hours) increased significantly, but was not affected by high intake of NaCl. The most significant decrease of plasma OA was observed during postdilution hemodiafiltration (63.3%).. Our study indicates that renal replacement therapy is not effective for a permanent reduction of elevated plasma levels of OA.

Topics: Adult; Ascorbic Acid; Atherosclerosis; Creatinine; Female; Glomerulonephritis; Humans; Kidney Diseases; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Oxalic Acid; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis; Uremia; Vitamin B 6

Oxidative stress is believed to contribute to the pathogenesis of hypercholesterolaemic atherosclerosis; hence, various antioxidant compounds are being evaluated for potential anti-atherogenic effects. The present study assessed the efficacy of epigallocatechin gallate (EGCG), an antioxidant component of the plant Camellia sinensis, in improving serum lipid profile and antioxidant parameters in erythrocytes and cardiac tissue in rats fed an atherogenic diet. In male albino Wistar rats fed an atherogenic diet for 30 days, significantly increased serum levels of total cholesterol, triglycerides and lipoprotein cholesterol fractions and cardiac risk ratio were noted, compared with levels in rats fed a normal diet. Intraperitoneal administration of EGCG (100 mg/kg) for 7 or 15 days to the atherogenic diet-fed rats resulted in significantly lower serum levels of total cholesterol, triglycerides, low-density and very low density lipoprotein cholesterol fractions and a significantly higher serum level of high-density lipoprotein cholesterol compared with levels in atherogenic diet-fed, saline-treated rats. Significantly higher mean malondialdehyde levels and significantly lower mean activities of antioxidant enzymes and mean levels of non-enzymatic antioxidants occurred in atherogenic diet-fed rats compared with those fed a normal diet. When atherogenic diet-fed rats received EGCG treatment for 7 or 15 days, significantly lower mean levels of MDA, higher mean levels of non-enzymatic antioxidants and higher mean activities of enzymatic antioxidants occurred, compared with those in saline-treated rats. Thus, EGCG appears to ameliorate disruptions of serum lipid profile and of antioxidant parameters in erythrocyte and cardiac tissue of Wistar rats fed an atherogenic diet; these results may be relevant to treating human atherosclerosis.

Topics: Animals; Anticholesteremic Agents; Antioxidants; Aorta, Thoracic; Ascorbic Acid; Atherosclerosis; Camellia sinensis; Catalase; Catechin; Diet, Atherogenic; Erythrocytes; Glutathione Peroxidase; Hypercholesterolemia; Injections, Intraperitoneal; Lipid Peroxidation; Lipids; Male; Oxidative Stress; Plant Extracts; Rats; Rats, Wistar; Superoxide Dismutase; Vitamin E

Certain drastic behavioral modifications by arterial wall smooth muscle cells (SMC) have been considered key steps in the formation of atherosclerotic lesions: massive migration of SMC from the media to the intima layer of the vessel, dedifferentiation of SMC to proliferating phenotype, and increased secretion of inflammatory cytokines as a response to inflammatory stimuli. We investigated the anti-atherogenic effects of naturally occurring compounds (ascorbic acid, green tea extract, lysine, proline, arginine, and N-acetyl cysteine) using the model of cultured aortic SMC. Cell growth was measured by DNA synthesis, cell invasiveness was measured through Matrigel, matrix metalloproteinase-2 (MMP-2) secretion was measured by zymography, and SMC secretion of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) was measured by immunochemistry. Fetal bovine serum-stimulated SMC growth was inhibited by the nutrient mixture (NM) with 85% inhibition at 100 microg/mL. A corresponding concentration of epigallocatechin gallate (EGCG; 15 microM), the most active tea phenolic, produced a significant effect but one lower than NM. NM inhibited aortic SMC Matrigel invasion in a dose-dependent manner and significantly decreased MMP-2 expression. Stimulation of SMC with tumor necrosis factor-alpha significantly increased production and secretion of such mediators of inflammation as IL-6 and MCP-1; addition of 100 microg/mL NM inhibited secretion of MCP-1 and IL-6 by 65% and 47%, respectively. These data suggest that the NM of ascorbic acid, tea phenolics, and selected amino acids has potential in blocking the development of atherosclerotic lesions by inhibiting atherogenic responses of vascular SMC to pathologic stimuli and warrants in vivo studies.

Topics: Amino Acids; Animals; Aorta; Ascorbic Acid; Atherosclerosis; Catechin; Cattle; Cell Proliferation; Cells, Cultured; Chemokine CCL2; Dose-Response Relationship, Drug; Humans; Immunochemistry; Interleukin-6; Matrix Metalloproteinase 2; Myocytes, Smooth Muscle; Phenols; Plant Extracts; Tea

When the availability of tetrahydrobiopterin (BH4) is deficient, endothelial nitric oxide synthase (eNOS) produces superoxide rather than NO (uncoupled eNOS). We have shown that the atherosclerotic lesion size was augmented in apolipoprotein E-deficient (ApoE-KO) mice overexpressing eNOS because of the enhanced superoxide production. In this study, we addressed the specific importance of uncoupled eNOS in atherosclerosis, and the potential mechanistic role for specific versus nonspecific antioxidant strategies in restoring eNOS coupling.. We crossed mice overexpressing eNOS in the endothelium (eNOS-Tg) with mice overexpressing GTP-cyclohydrolase I (GCH), the rate-limiting enzyme in BH4 synthesis, to generate ApoE-KO/eNOS-Tg/GCH-Tg mice. As a comparison, ApoE-KO/eNOS-Tg mice were treated with vitamin C. Atherosclerotic lesion formation was increased in ApoE-KO/eNOS-Tg mice compared with ApoE-KO mice. GCH overexpression in ApoE-KO/eNOS-Tg/GCH-Tg mice increased vascular BH4 levels and reduced plaque area. This reduction was associated with decreased superoxide production from uncoupled eNOS. Vitamin C treatment failed to reduce atherosclerotic lesion size in ApoE-KO/eNOS-Tg mice, despite reducing overall vascular superoxide production.. In contrast to vitamin C treatment, augmenting BH4 levels in the endothelium by GCH overexpression reduced the accelerated atherosclerotic lesion formation in ApoE-KO/eNOS-Tg mice, associated with a reduction of superoxide production from uncoupled eNOS.

Topics: Analysis of Variance; Animals; Antioxidants; Apolipoproteins E; Ascorbic Acid; Atherosclerosis; Biopterins; Disease Models, Animal; Endothelium, Vascular; Female; GTP Cyclohydrolase; Mice; Mice, Inbred C57BL; Nitric Oxide Synthase Type III; Probability; Reactive Oxygen Species; Sensitivity and Specificity; Superoxides

Topics: Antioxidants; Ascorbic Acid; Atherosclerosis; Ferritins; Hemoglobins; Humans; Inflammation; Iron; Kidney Failure, Chronic; Oxidants; Oxidative Stress; Renal Dialysis

Topics: Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Atherosclerosis; C-Reactive Protein; Dose-Response Relationship, Drug; Endothelium, Vascular; Fruit; Humans; Vegetables

Understanding the mechanisms involved in oxidative stress-induced foam cell formation is of fundamental importance for atherosclerosis. Our aim was to characterize the effects of oxidative stress on key receptors of macrophage cholesterol homeostasis, on the nuclear transcription factors PPAR and LXR regulating their expression, and on macrophage cholesterol handling.. The incubation of macrophages derived from the human monocyte cell line THP-1 with iron (100 microm)/ascorbate (1000 microm) for a period of 4 h induced a strong peroxidation, as demonstrated by the elevation of malondialdehyde (220%, P < 0.001). The production of lipid peroxidation affected cholesterol efflux, which was probably due to decreased ABCAI gene and protein expression. On the other hand, cholesterol influx remained unchanged as did the mRNA and protein levels of SR-BI and CD36, important protein receptors that participate in cholesterol import. Experiments using RT-PCR showed that the ABCAI modulation was orchestrated by the nuclear receptors LXRalpha, LXRbeta, PPARalpha, and PPARgamma. Treatment with powerful antioxidants (Trolox and BHT) prevented the adverse effects of iron-ascorbate on cholesterol movement, conceivably supporting the role of oxidative stress.. Our results show that oxidative stress can directly be induced in macrophages and concomitantly impairs the expression of receptors involved in cholesterol flux, which could influence foam cell formation and atherosclerosis development.

Topics: Antioxidants; Ascorbic Acid; Atherosclerosis; ATP Binding Cassette Transporter 1; ATP-Binding Cassette Transporters; Blotting, Western; Butylated Hydroxytoluene; CD36 Antigens; Cell Line; Cholesterol; Chromans; DNA-Binding Proteins; Foam Cells; Gene Expression; Homeostasis; Humans; Lipid Peroxidation; Liver X Receptors; Orphan Nuclear Receptors; Oxidative Stress; Peroxisome Proliferator-Activated Receptors; PPAR alpha; PPAR gamma; PPAR-beta; Receptors, Cytoplasmic and Nuclear; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Scavenger Receptors, Class B

Topics: Animals; Aorta; Arteriosclerosis; Ascorbic Acid; Atherosclerosis; Blood Proteins; Cholesterol; Chromium Isotopes; Dietary Fats; Hypercholesterolemia; Lipid Metabolism; Liver; Rabbits; Research

Topics: Aging; Aortic Diseases; Arteriosclerosis; Ascorbic Acid; Atherosclerosis; Calcium; Hexosamines; Histocytochemistry; Hydroxyproline; Lipidoses; Lipids; Pathology; Research

Topics: Arteriosclerosis; Ascorbic Acid; Ascorbic Acid Deficiency; Atherosclerosis; Biomedical Research; Drug Therapy; Humans; Vitamins

Topics: Arteriosclerosis; Ascorbic Acid; Atherosclerosis; Cholesterol; Gastric Mucins; Humans; Lipids; Niacinamide; Pyridoxine; Vitamin A; Vitamins

Topics: Arteriosclerosis; Ascorbic Acid; Atherosclerosis; Cholesterol; Humans

Topics: Ascorbic Acid; Atherosclerosis; Cholesterol; Humans; Hypercholesterolemia

Topics: Arteriosclerosis; Ascorbic Acid; Atherosclerosis; Humans; Methionine; Phenobarbital; Pyridoxine

Topics: Arteriosclerosis; Ascorbic Acid; Atherosclerosis; Basal Metabolism; Corrinoids; Hematinics; Humans; Vitamin B 12; Vitamin B Complex; Vitamins

Topics: Arteriosclerosis; Ascorbic Acid; Atherosclerosis; Essential Hypertension; Humans; Hypertension; Lipids

Topics: Arteriosclerosis; Ascorbic Acid; Atherosclerosis; Humans; Iodides; Iodine; Thyroid Gland; Viscera; Vitamins

Topics: Animals; Arteriosclerosis; Ascorbic Acid; Atherosclerosis; Chickens; Meat; Vitamins

Topics: Ascorbic Acid; Atherosclerosis; Cholesterol; Humans; Vitamins

Topics: Ascorbic Acid; Atherosclerosis; Humans; Lipoproteins; Vitamins

Topics: Arteriosclerosis; Ascorbic Acid; Atherosclerosis; Choline; Fibrinogen; Humans; Iodine; Prothrombin; Vitamins

Topics: Arteriosclerosis; Ascorbic Acid; Atherosclerosis; Iodine

Topics: Acid-Base Equilibrium; Arteriosclerosis; Ascorbic Acid; Atherosclerosis; Cholesterol; Humans; Hypertension; Vitamins

Topics: Arteriosclerosis; Ascorbic Acid; Atherosclerosis; Humans; Vitamins

Topics: Arteriosclerosis; Ascorbic Acid; Atherosclerosis; Cholesterol; Humans; Vitamin B 12; Vitamins

Topics: Arteriosclerosis; Ascorbic Acid; Atherosclerosis; Biomedical Research; Humans; Vitamins

Topics: Arteriosclerosis; Ascorbic Acid; Atherosclerosis; Tunica Intima

Topics: Arteriosclerosis; Ascorbic Acid; Atherosclerosis; Humans; Vitamin A; Vitamins

Topics: Arteriosclerosis; Ascorbic Acid; Atherosclerosis; Blood; Cholesterol; Humans; Hypertension; Vitamins