stilbenes and Arteriosclerosis

Aging is a major risk factor for the development of cardiovascular disease. Despite a significant reduction in the mortality and morbidity rates over the last decade, the socio-economic burden of cardiovascular disease is still substantial. Consequently, there is a considerable need for alternative strategies, such as nutraceutical supplementation, that delay the functional vascular decline present in the elderly. Compromised autophagy and oxidative stress (OS) are considered major causes of the age-related endothelial dysfunction. OS reduces the bioavailability of nitric oxide (NO), which has been associated with hypertension, arteriosclerosis, and a reduced vasodilatory response. High levels of free radicals and the low bioavailability of NO lead to a positive feedback loop of further OS, organelle damage, poor repair, and endothelial dysfunction. Here we draw attention to the relationship between OS and autophagy in the aged vasculature. We have reviewed the published literature and provided arguments that support that treatment with resveratrol stimulates autophagy and thereby has the potential to restore oxidative balance in the endothelium, which indicates that treatment with resveratrol might have therapeutic potential to restore endothelial function in the elderly.

Topics: Aging; Animals; Antioxidants; Arteriosclerosis; Autophagy; Endothelium, Vascular; Humans; Hypertension; Nitric Oxide; Oxidative Stress; Resveratrol; Stilbenes

The role of inflammation and oxidative stress in atherosclerosis development has been increasingly well recognized over the past decade. Inflammation has a significant role at all stages of atherosclerosis, including initiation, progression and plaque formation. Resveratrol is a naturally occurring polyphenolic compound found in grape products, berry fruits and red wine. Its ability to behave therapeutically as a component of red wine has attracted wide attention. Accumulating evidence suggests that it is a highly pleiotropic molecule that modulates numerous targets and molecular functions. Epidemiological studies indicate that the Mediterranean diet, rich in resveratrol, is associated with a reduced risk of atherosclerosis. Resveratrol is believed to decrease circulating low-density lipoprotein cholesterol levels, reduce cardiovascular disease risk; it reduces lipid peroxidation, platelet aggregation and oxidative stress. Resveratrol is considered a safe compound, since no significant toxic effects have been demonstrated after administration of a broad range of concentrations, and an effective anti-atherogenic agent.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arteriosclerosis; Humans; Resveratrol; Stilbenes

We review evidence for and against the 'red wine hypothesis', whereby red wine is more likely to confer cardiovascular benefits than white. As background, there is a strong epidemiological and mechanistic evidence for J-shaped relation between alcohol intake and total mortality. However, epidemiological data favouring a specific benefit of red over white wine are not strong and the 'French paradox' could at least in part be explained by confounding factors. More convincing evidence is that human studies with de-alcoholized red but not white wine show short-term cardiovascular benefits. The specific components of the de-alcoholized wine that are active on cardiovascular endpoints, are the polyphenols found in red wine, especially resveratrol. The effects of resveratrol on isolated tissues or organs are well-described including molecular mechanisms leading to decreased arterial damage, decreased activity of angiotensin-II, increased nitric oxide, and decreased platelet aggregation. Anti-ischaemic effects include stimulation of prosurvival paths, decreased LDL-oxidation, atheroma, and on the ischaemic-beneficial metabolic changes. Most recently, the agonist effect of resveratrol on the anti-senescence factor sirtuin has lessened cell death in myocytes from failing hearts. Mechanistic feasibility strengthens the case for prospective therapeutic trials of alcohol vs. red wine vs. resveratrol, for example in those with heart failure.

Topics: Alcohol Drinking; Animals; Arteriosclerosis; Coronary Disease; Female; Flavonoids; Humans; Hypertension; Male; Mice; Phenols; Platelet Aggregation; Platelet Aggregation Inhibitors; Polyphenols; Rats; Resveratrol; Risk Factors; Stilbenes; Wine

Cardiovascular diseases are the leading cause of death in developed countries where the common pathological substrate underlying this process is atherosclerosis. Several new concepts have emerged in relation to mechanisms that contribute to the regulation of the vascular diseases and associated inflammatory effects. Recently, potential antioxidants (vitamin E, polyphenols) have received much attention as potential anti-atherosclerotic agents. Among the polyphenols with health benefic properties, resveratrol, a phytoalexin of grape, seem to be a good candidate protecting the vascular walls from oxidation, inflammation, platelet aggregation, and thrombus formation. In this review, we focus on the mechanism of resveratrol cardiovascular benefic effects. We analyze, in relation with the different steps of atherosclerotic process, the resveratrol properties at multiple levels, such as cellular signaling, enzymatic pathways, apoptosis, and gene expression. We show and discuss the relationship with reactive oxygen species, regulation of pro-inflammatory genes including cycloxygenases and cytokines in molecular inflammatory and aging processes, and how the regulation of these activites by resveratrol can lead to a prevention of vascular diseases.

Topics: Aging; Arteriosclerosis; Cardiovascular Diseases; Foam Cells; Health Promotion; Humans; Lipoproteins; Macrophages; Muscle, Smooth, Vascular; Neovascularization, Pathologic; Oxidative Stress; Platelet Aggregation; Resveratrol; Stilbenes; Vasodilation

Topics: Animals; Antioxidants; Arteriosclerosis; Cardiovascular Agents; Humans; Myocardial Reperfusion Injury; Platelet Aggregation Inhibitors; Resveratrol; Stilbenes; Vasodilator Agents

Topics: Animals; Anticarcinogenic Agents; Antioxidants; Arteriosclerosis; Biological Availability; Cell Division; Gene Transfer, Horizontal; Humans; Inflammation; Intestinal Absorption; Neoplasms; Resveratrol; Stilbenes; Vitis

Resveratrol (3, 4', 5 trihydroxystilbene) is a naturally occuring phytoalexin produced by some spermatophytes, such as grapevines, in response to injury. Given that it is present in grape berry skins but not in flesh, white wine contains very small amounts of resveratrol, compared to red wine. The concentrations in the form of trans- and cis- isomers of aglycone and glucosides are subjected to numerous variables. In red wine, the concentrations of the trans-isomer, which is the major form, generally ranges between 0.1 and 15 mg/L. As phenolic compound, resveratrol contributes to the antioxidant potential of red wine and thereby may play a role in the prevention of human cardiovascular diseases. Resveratrol has been shown to modulate the metabolism of lipids, and to inhibit the oxidation of low-density lipoproteins and the aggregation of platelets. Moreover, as phytoestrogen, resveratrol may provide cardiovascular protection. This compound also possesses anti-inflammatory and anticancer properties. However, the bioavailability and metabolic pathways must be known before drawing any conclusions on the benefits of dietary resveratrol to health.

Topics: Anticarcinogenic Agents; Antioxidants; Arteriosclerosis; Humans; Resveratrol; Rosales; Stilbenes; Wine

The role of resveratrol (trans-3,5,4'-trihydroxystilbene; RES) in lysophosphatidylcholine (LPC)‑induced injury and inflammation in endothelial cells (regarded as an early event in arteriosclerosis) is unclear. The present study investigated whether RES reduces lactate dehydrogenase (LDH) activity and secretion of inflammatory cytokines such asinterleukin‑6 and tumor necrosis factor‑α, via the Toll‑like receptor (TLR)‑4/myeloid differentiation primary response gene 88 (MyD88)/nuclear factor (NF)‑κB signal transduction pathway in LPC‑induced damage and inflammation in human umbilical vein endothelial‑12 (HUVE‑12) cells. Using an ELISA and western blotting, the present study investigated the effects of RES on LDH activity and cytokine secretion. The effects of TLR‑4 short hairpin (sh)RNA and TLR‑4 cDNA transfection on NF‑κB activation during LPC‑induced damage and inflammation was also investigated in HUVE‑12 cells. The results demonstrated that RES significantly inhibited the effect of LPC on enzyme activity, pro‑inflammatory cytokine secretion, and expression of TLR‑4, MyD88 and NF‑κBp65 expression. In addition, RES and TLR‑4 shRNA transfection suppressed LPC‑induced injury and inflammation by blocking the TLR‑4/MyD88/NF‑κB signaling pathway Conversely, transfection with TLR‑4 cDNA enhanced LPC‑induced injury and inflammation, which abrogated the protective effects of RES. These data suggested that RES significantly suppressed LPC‑induced damage and inflammation, via suppression of the TLR‑4/MyD88/NF‑κB signaling pathway, which may provide a new mechanistic evidence for the treatment of arteriosclerosis by RES.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arteriosclerosis; Cell Line; DNA, Complementary; Gene Expression Regulation; Human Umbilical Vein Endothelial Cells; Humans; Interleukin-6; L-Lactate Dehydrogenase; Lysophosphatidylcholines; Models, Cardiovascular; Myeloid Differentiation Factor 88; NF-kappa B; Resveratrol; RNA, Small Interfering; Signal Transduction; Stilbenes; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

This study was performed to investigate the hypolipidemic, antiobese, and antiatherogenic effects of resveratrol in apoE-deficient mice fed an atherogenic diet (20% fat and 1% cholesterol). These animals were fed an atherogenic diet containing 0.02% lovastatin (w/w) or 0.02% resveratrol (w/w) for 12 weeks. Resveratrol and lovastatin supplementation significantly reduced either the body weight or epididymal fat weight without altering the food intake and food efficiency ratio. Resveratrol significantly decreased the plasma total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C) concentrations, apoB/apoA-I ratio, hepatic cholesterol, and triglyceride (TG) contents, whereas significantly it increased the plasma HDL-C concentration compared with the control and lovastatin groups. Plasma and hepatic TG and plasma apoB levels were significantly lower in both the lovastatin and resveratrol groups than in the control group without altering the plasma apoA-I concentration. Both resveratrol and lovastatin significantly decreased hepatic fatty acid and TG synthesis, whereas they increased fatty acid oxidation (β-oxidation) except for the carnitine palmitoyltransferase activity compared with the control group. However, there was no difference in hepatic 3-hydroxyl-3-methylglutaryl-CoA reductase activity among the groups, although hepatic acyl-CoA: cholesterol acyltransferase activity was significantly lower in the lovastatin groups than in the control group. In epididymal adipose tissue, resveratrol supplementation led to an increase in β-oxidation and decrease in TG synthesis, compared with the control group. Tissue morphology revealed that there were dramatic decreases in hepatic lipid droplets and aortic fatty streaks by resveratrol and lovastatin supplementation. This study demonstrates that resveratrol exerts not only antiobesity and hypolipidemic effects, but also protective effects for the liver and aorta through the modulation of lipid metabolism in both the liver and white adipose tissues.

Topics: Animals; Anti-Obesity Agents; Anticholesteremic Agents; Aorta; Apolipoproteins E; Arteriosclerosis; Diet, Atherogenic; Humans; Lovastatin; Male; Mice; Mice, Knockout; Obesity; Protective Agents; Resveratrol; Stilbenes

The content of resveratrol is relatively high in Polygonum cuspidatum Sieb. et Zucc., and the resveratrol has the effect of blood vessel dilating, microcirculation improving, platelet aggregation inhibiting and anti-cancer. The objective of this paper was to study the effect of resveratrol on lipid metabolism in hyperlipidemia mice.. Through the establishment of an experimental mouse model of hyperlipidemia, the effect of resveratrol on change in total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c) levels in mouse serum were determined.. Resveratrol group can apparently reduce TC, TG, LDL-c and AI of hyperlipidemic mice in a dose effect manner.. We concluded that resveratrol can effectively reduce blood lipid levels of hyperlipidemic mice.

Topics: Animals; Arteriosclerosis; Cholesterol; Dose-Response Relationship, Drug; Fallopia japonica; Hyperlipidemias; Lipid Metabolism; Male; Mice; Phytotherapy; Plant Extracts; Resveratrol; Stilbenes; Triglycerides

The present study examined the efficacy of using longevinex, a commercially available resveratrol formulation, to lower blood cholesterol in hypercholesteromic rabbits. New Zealand white rabbits were randomly divided into two groups (n = 6 per group), one group was given high cholesterol diet for 3 months while the other group fed regular diet served as control. The high cholesterol diet fed group was further subdivided into two groups (n = 6 per group), one group was given longevinex resveratrol while the other group given vehicle only served as control. Longevinex was given by gavaging up to a period of 6 months. Longevinex-treated rabbits exhibited lowering of plasma cholesterol level. Inhibition of arterial plaque formation was noticed even after 1 month. Longevinex-treated hearts demonstrated improved ventricular recovery when isolated working hearts were subjected to 30 min of ischemia followed by 2 h of reperfusion. Aortic flow and developed pressure during post-ischemic reperfusion period were significantly higher for the longevinex-treated hearts compared to those in control group of hearts. Myocardial infarct size was also lower in the treated group compared to that for the untreated group. These results indicate cholesterol-lowering ability of longevinex, which appears to reflect in its ability to protect the hypercholesteromic hearts from ischemic reperfusion injury.

Topics: Animals; Anticholesteremic Agents; Arteriosclerosis; Biomarkers; Cholesterol; Disease Models, Animal; Down-Regulation; Hemodynamics; Hypercholesterolemia; Male; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Rabbits; Resveratrol; Stilbenes; Time Factors; Ventricular Function, Left; Ventricular Pressure

Topics: Alcohol Drinking; Animals; Antioxidants; Arteriosclerosis; Cohort Studies; Cricetinae; Dose-Response Relationship, Drug; Female; Fibrinolytic Agents; Flavonoids; Follow-Up Studies; Gene Expression Regulation; Humans; Male; Middle Aged; Myocardial Infarction; Phenols; Phytotherapy; Polyphenols; Rabbits; Resveratrol; Risk; Stilbenes; Stroke; Wine

The effects of the phenolic compounds catechin (Cat), quercetin (Qer), and resveratrol (Res) present in red wine on early atherosclerosis were studied in hamsters. Hamsters (n = 32) were divided into 4 groups of 8 and fed an atherogenic diet for 12 weeks. They received by force-feeding 7.14 mL/(kg of body wt.day) Cat, Qer, or Res in water [2.856 mg/(kg of body wt.day) for Cat and 0.1428 mg/(kg of body wt.dday) for Qer and Res], mimicking a moderate consumption of alcohol-free red wine (equivalent to that supplied by the consumption of about two glasses of red wine per meal for a 70 kg human), or water as control. Plasma cholesterol concentration was lower in groups that consumed phenolics than in controls. The increase in plasma apolipoprotein (Apo) A1 concentration was mainly due to Cat (26%) and Qer (22%) and to a lesser extent, but nonsignificantly, Res (19%). Apo-B was not affected. Plasma antioxidant capacity was not improved, and there was no sparing effect on plasma vitamins A and E. Plasma iron and copper concentrations were not modified nor were liver super oxide dismutase and catalase activities. A sparing effect of Qer on liver glutathione peroxidase activity appeared, whereas Cat and Res exhibited a smaller effect. Aortic fatty streak area was significantly reduced in the groups receiving Cat (84%) or Qer (80%) or Res (76%) in comparison with the controls. These findings demonstrate that catechin, quercetin, and resveratrol at nutritional doses prevent the development of atherosclerosis through several indirect mechanisms.

Topics: Animals; Aortic Diseases; Arteriosclerosis; Catechin; Cricetinae; Disease Models, Animal; Hypercholesterolemia; Male; Mesocricetus; Quercetin; Resveratrol; Stilbenes; Wine

There seems to be a link between the cluster of risk factors known as insulin resistance syndrome with endothelial dysfunction. Resveratrol (3,4,5-trihydroxyestilbene) (RV), an antioxidant found in many components of the human diet, has been proposed as an effective agent in the prevention of several pathologic processes. This study examined the effect of chronic administration of RV on endothelial nitric oxide synthase (eNOS) activity in cardiovascular tissues and on plasma lipid peroxidation in fructose-fed rats (FFR), an experimental model of this syndrome.. Male Sprague Dawley rats were separated into four groups: Control, Control + RV, FFR, and FFR + RV (n = 8 in each group). The RV (10 mg/kg/d by gavage) and fructose (10% in drinking water) were administered for 45 days. Metabolic variables and systolic blood pressure (BP) were measured. The eNOS activity was estimated in the mesenteric arterial bed and cardiac tissue homogenates by conversion of (3)H-arginine to (3)H-citrulline. Lipid peroxidation was estimated through the measurement of plasmatic thiobarbituric acid-reactive substances (TBARS).. The RV chronic treatment prevented the increase in systolic BP and cardiac hypertrophy, restored FFR mesenteric and cardiac eNOS activities, and decreased the elevated TBARS levels that characterize FFR, without an effect on other metabolic variables.. In concert with other effects, the increase in eNOS activity may contribute to the protective properties attributed to RV and, thus, to its beneficial effects on the cardiovascular system. These results suggest that an adequate supplementation of RV might help to prevent or delay the occurrence of atherogenic cardiovascular diseases associated to insulin-resistant states.

Topics: Administration, Oral; Animal Feed; Animals; Antioxidants; Arteriosclerosis; Biomarkers; Blood Pressure; Follow-Up Studies; Fructose; Heart Ventricles; Hypertension; Insulin Resistance; Lipid Peroxidation; Male; Mesenteric Arteries; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Rats; Rats, Sprague-Dawley; Resveratrol; Risk Factors; Spectrophotometry; Stilbenes; Sweetening Agents; Thiobarbituric Acid Reactive Substances; Time Factors

Resveratrol is one of the major polyphenolics in red wine that has been shown to exert the preventive effects against cardiovascular diseases. The effect of trans-resveratrol (t-RES) administered as an ingredient of the diet on the atherothrombotic tendency was assessed in genetically hypercholesterolemic mice after laser-induced damage on endothelium. Mice lacking both apolipoprotein E and low-density lipoprotein receptor (apoE-/-/LDLR-/-) were fed with a high-fat diet with or without t-RES (9.6 and 96 mg/kg diet) for 8 weeks. The atherosclerotic tendency was morphometrically analyzed in their aortae. The thrombotic tendency was determined by inducing thrombus by the irradiation of a helium-neon laser on carotid arteries of these mice with injection of Evans blue. Atherosclerotic area and thrombus size were evaluated by image analyzing in a computer system. Even though the plasma concentrations of lipids (total cholesterol and triacylglycerol) did not change in the control and t-RES groups, a significant decrease (approximately 30%) in the formation of atheroma was observed in the aortae of the t-RES group. The size of laser-induced thrombus that mostly consisted of platelet aggregates was significantly reduced (approximately 25%) in the t-RES group compared with that in the control group. Thus, t-RES orally administrated with a high-fat diet in apoE-/-/LDLR-/- mice significantly suppressed atherosclerosis in their aortae and reduced the laser-induced thrombosis in their carotid arteries.

Topics: Animals; Aortic Diseases; Apolipoproteins E; Arteriosclerosis; Carotid Artery Thrombosis; Cholesterol; Diet, Atherogenic; Dietary Fats; Drug Evaluation, Preclinical; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Platelet Aggregation; Radiation Injuries, Experimental; Receptors, LDL; Resveratrol; Stilbenes; Thrombophilia; Triglycerides

Epidemiology suggests that Mediterranean diets are associated with reduced risk of cardiovascular disease. Because monocyte adhesion to the endothelium is crucial in early atherogenesis, we evaluated whether typical olive oil and red wine polyphenols affect endothelial-leukocyte adhesion molecule expression and monocyte adhesion.. Phytochemicals in olive oil and red wine, including oleuropein, hydroxytyrosol, tyrosol, elenolic acid, and resveratrol, with or without antioxidant activity, were incubated with human umbilical vein endothelial cells for 30 minutes, followed by co-incubation with bacterial lipopolysaccharide or cytokines to trigger adhesion molecule expression. At nutritionally relevant concentrations, only oleuropein, hydroxytyrosol, and resveratrol, possessing a marked antioxidant activity, reduced monocytoid cell adhesion to stimulated endothelium, as well as vascular cell adhesion molecule-1 (VCAM-1) mRNA and protein by Northern analysis and cell surface enzyme immunoassay. Reporter gene assays with deletional VCAM-1 promoter constructs indicated the relevance of nuclear factor-kappaB, activator protein-1, and possibly GATA binding sites in mediating VCAM-1 transcriptional inhibition. The involvement of nuclear factor-kappaB and activator protein-1 was finally demonstrated at electrophoretic mobility shift assays.. Olive oil and red wine antioxidant polyphenols at nutritionally relevant concentrations transcriptionally inhibit endothelial adhesion molecule expression, thus partially explaining atheroprotection from Mediterranean diets.

Topics: Animals; Antioxidants; Arteriosclerosis; Cattle; Cell Adhesion; Cells, Cultured; Diet; Endothelium, Vascular; Flavonoids; Gene Expression Regulation; Humans; Iridoid Glucosides; Iridoids; NF-kappa B; Olive Oil; Phenols; Phenylethyl Alcohol; Plant Oils; Polyphenols; Pyrans; Resveratrol; RNA, Messenger; Stilbenes; Transcription Factor AP-1; Transcription, Genetic; U937 Cells; Vascular Cell Adhesion Molecule-1; Wine

Low or moderate consumption of red wine has a greater benefit than the consumption of other beverages in the prevention of atherosclerosis and coronary heart disease and this is increasingly attributed to the polyphenol compounds in red wine, such as resveratrol. In the present study, we investigated the effect of resveratrol on platelet aggregation in vitro and in vivo.. Platelet aggregation in rabbits and normal subjects was measured using Born's method.. Resveratrol, at 10 - 1000 micromol/L, significantly inhibited platelet aggregation in vitro induced by collagen, thrombin, and ADP in healthy subjects. The inhibitory effect was concentration-dependent. Hypercholesterolemia induced by high-cholesterol diet enhanced ADP-induced platelet aggregation. Resveratrol 4 mg x kg(-1) x d(-1) inhibited ADP-induced platelet aggregation in vivo despite no changes in serum lipid levels.. Resveratrol inhibits platelet aggregation both in vitro and in vivo. This may be one of the mechanisms by which resveratrol prevents atherosclerosis.

Topics: Animals; Arteriosclerosis; Cholesterol, LDL; Humans; Lipids; Platelet Aggregation; Platelet Aggregation Inhibitors; Rabbits; Resveratrol; Stilbenes

The hypothesis was tested that resveratrol, a compound in red wine, would inhibit atherosclerotic development in rabbits fed 0.5% cholesterol for 60 days. Rabbits were supplemented with or without oral resveratrol. During the study, body weights and food consumption were similar for the two groups. The lack of differences between liver weights and a series of serum parameters indicative of liver disease suggest that liver function was similar in the two groups. The diet produced hypercholesterolemia in both groups, but no differences in lipoprotein-cholesterol concentrations. The electrophoretic mobility of plasma low-density lipoprotein (LDL) and plasma LDL after induced oxidation also was not different between the groups. Staining of atherosclerotic lesions in the control and resveratrol-treated groups revealed that the resveratrol-treated rabbits had significantly more aortic surface area covered by atherosclerotic lesions (P < 0.02). Therefore, resveratrol promoted atherosclerotic development, rather than protect against it, by a mechanism that is independent of observed differences in gross animal health, liver function, plasma cholesterol concentrations, or LDL oxidative status.

Topics: Animals; Aorta; Arteriosclerosis; Disease Models, Animal; Kidney; Lipoproteins; Liver; Male; Platelet Aggregation Inhibitors; Rabbits; Resveratrol; Stilbenes

A number of lines of evidence suggest that red wine may be more effective than other alcoholic beverages in decreasing the risk of coronary heart disease (CHD) mortality. This protection over and above that due to ethanol itself may be explained by phenolic components with which red wines are richly endowed. We have studied the effects of the trihydroxy stilbene trans-resveratrol on human platelet aggregation and on the synthesis of three eicosanoids from arachidonate by platelets, i.e. thromboxane B2 (TxB2), hydroxyheptadecatrienoate (HHT) and 12-hydroxyeicosatetraenoate (12-HETE). These effects were compared with the actions of other wine phenolics (quercetin, catechin and epicatechin) and antioxidants (alpha-tocopherol, hydroquinone and butylated hydroxytoluene). trans-Resveratrol and quercetin demonstrated a dose-dependent inhibition of both thrombin-induced and ADP-induced platelet aggregation, whereas ethanol inhibited only thrombin-induced aggregation. The other compounds tested were inactive. trans-Resveratrol also inhibited the synthesis of TxB2, HHT, and to a lesser extent 12-HETE, from arachidonate in a dose-dependent manner. Quercetin inhibited only 12-HETE synthesis, and hydroquinone caused slight inhibition of TxB2 synthesis, the remaining compounds being ineffective. De-alcoholized red wines inhibited platelet aggregation; their ability to inhibit the synthesis of TxB2 but not that of 12-HETE from labelled arachidonate by washed human platelets was proportional to their trans-resveratrol concentration. These results are consistent with the notion that trans-resveratrol may contribute to the presumed protective role of red wine against atherosclerosis and CHD.

Topics: Arteriosclerosis; Coronary Disease; Eicosanoids; Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Quercetin; Resveratrol; Stilbenes; Wine

Glutathione transferases play an important role in the detoxification of many different endogeneous and exogenous compounds such as metabolites of polycyclic aromatic hydrocarbons (PAH) of cigarette tar. There is evidence that PAH may be atherogenic. The glutathione transferase activity towards trans-stilbene oxide (GST-tSBO) can be separated in blood in GST-positive and GST-negative phenotypes. We have previously suggested that the GST-negative phenotype may be associated with a higher morbidity in intermittent claudication among middle aged smokers. In the present study, GST-tSBO could easily be measured in human, rabbit and bovine arterial smooth muscle cells (SMC) in culture. The level of GST-tSBO was higher in rabbit than in bovine SMC. It was stable in bovine SMC during 5 cell passages and it could be induced twofold by long-time incubation with dimethylsulfoxide-soluble particulate matter from cigarette smoke or 3,4-benzo(a)pyrene. There was a positive correlation between the level of GST-tSBO in blood and in "healthy" arterial and venous tissue from individuals operated with coronary bypass. The enzyme levels in arterial tissue were lower than in venous tissue. GST-tSBO in atherosclerotic segments of human arteries was lower than in "healthy" segments from the same artery. These findings suggest that the arterial wall may have a low defense against toxic compounds that may decrease further as atherosclerosis proceeds. It is concluded that SMC are suitable for the study of the effects of PAH in relation to GST-tSBO and that the enzyme activity in blood will reflect the individual GST-tSBO phenotype also in vascular tissues.

Topics: Adult; Animals; Arteriosclerosis; Cattle; Cells, Cultured; Female; Glutathione Transferase; Humans; In Vitro Techniques; Male; Middle Aged; Muscle, Smooth, Vascular; Phenotype; Polycyclic Compounds; Rabbits; Smoking; Stilbenes

Topics: Adrenal Cortex Hormones; Adult; Androgens; Arteriosclerosis; Clofibrate; Coronary Disease; Female; Humans; Hypertension; Hypopituitarism; Nitroglycerin; Pregnancy; Puerperal Disorders; Radiography; Renal Artery Obstruction; Stilbenes; Thyroid Hormones

Topics: Androgens; Arteriosclerosis; Contraceptive Agents; Contraceptives, Oral; Coronary Disease; Diethylstilbestrol; Estradiol; Estrogens, Conjugated (USP); Ethinyl Estradiol; Female; Humans; Menopause; Methyltestosterone; Osteoporosis; Stilbenes; Surgical Procedures, Operative; Toxicology

Topics: Animals; Aortic Diseases; Arteriosclerosis; Chickens; Cholesterol; Coronary Disease; Diethylstilbestrol; Hexestrol; Stilbenes

Topics: Animals; Arteriosclerosis; Atherosclerosis; Chickens; Cholesterol; Diet; Humans; Stilbenes