gamma-sitosterol and Atherosclerosis

For years food consumers have been warned that a cholesterol-rich diet may result in atherosclerosis. It is also well known that consumption of large amounts of phytosterols decreases concentration of low-density lipoproteins (LDLs) in blood (LDLs are regarded a key risk factor in development of cardiovascular diseases). However, no scientific evidence has unambiguously proved any direct connection between amount of consumed cholesterol and LDL level in blood. On the other hand, concentration of cholesterol oxidation products, oxysterols, seems to be indeed relevant; for example, they significantly impact appearance of atherosclerotic lesions (plaques). Phytosterols (like sitosterol or campasterol) decrease LDL level in blood, but on the other hand products of their oxidation are toxic. Therefore, it is worth to know influence of phytosterols on living organisms, processes which lead to their formation, and their levels in popular foodstuffs. This paper is an attempt to review literature data on the above aspects, as well as on impact on living organisms of oxidation products of popular sterols.

Topics: Animals; Atherosclerosis; Cardiovascular Diseases; Cholesterol; Cholesterol, Dietary; Humans; Lipoproteins, LDL; Mice; Oxidation-Reduction; Oxysterols; Phytosterols; Risk Factors; Sitosterols

Patients undergoing vascular surgery are a high-risk population with widespread atherosclerosis, an adverse cardiovascular risk profile and often multiple co-morbidities. Postoperative cardiovascular complications, including myocardial infarct (MI), are common. Statins are the medical treatment of choice to reduce high cholesterol levels. Evidence is accumulating that patients taking statins at the time of surgery are protected against a range of perioperative complications, but the specific benefits for patients undergoing noncardiac vascular surgery are not clear.. We examined whether short-term statin therapy, commenced before or on the day of noncardiac vascular surgery and continuing for at least 48 hours afterwards, improves patient outcomes including the risk of complications, pain, quality of life and length of hospital stay. We also examined whether the effect of statin therapy on these outcomes changes depending on the dose of statin received.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 7), MEDLINE via Ovid SP (1966 to August 2012), EMBASE via Ovid SP (1966 to August 2012), CINAHL via EBSCO host (1966 to August 2012) and ISI Web of Science (1946 to July 2012) without any language restriction. We used a combination of free text search and controlled vocabulary search. The results were limited to randomized controlled clinical trials (RCTs). We conducted forwards and backwards citation of key articles and searched two clinical trial Websites for ongoing trials (www.clinicaltrials.gov and http://www.controlled-trials.com).. We included RCTs that had compared short-term statin therapy, either commenced de novo or with existing users randomly assigned to different dosages, in adult participants undergoing elective and emergency noncardiac arterial surgery, including both open and endovascular procedures. We defined short-term as commencing before or on the day of surgery and continuing for at least 48 hours afterwards.. Two authors independently assessed trial quality and extracted data, including information on adverse events. We contacted study authors for additional information. We performed separate analyses for the comparisons of statin with placebo/no treatment and between different doses of statin. We presented results as pooled risk ratios (RRs) with 95% confidence intervals (CIs) based on random-effects models (inverse variance method). We employed the Chi(2) test and calculated the I(2) statistic to investigate study heterogeneity.. We identified six eligible studies in total. The six Included studies were generally of high quality, but the largest eligible study was excluded because of concerns about its validity. Study populations were statin naive, which led to a considerable loss of eligible participants.Five RCTs compared statin use with placebo or standard care. We pooled results from three studies, with a total of 178 participants, for mortality and non-fatal event outcomes. In the statin group, 7/105 (6.7%) participants died within 30 days of surgery, as did 10/73 (13.7%) participants in the control group. Only one death in each group was from cardiovascular causes, with an incidence of 0.95% in statin participants and 1.4% in control participants, respectively. All deaths occurred in a single study population, and so effect estimates were derived from one study only. The risk ratio (RR) of all-cause mortality in statin users showed a non-significant decrease in risk (RR 0.73, 95% CI 0.31 to 1.75). For cardiovascular death, the risk ratio was 1.05 (95% CI 0.07 to 16.20). Non-fatal MI within 30 days of surgery was reported in three studies and occurred in 4/105 (3.8%) participants in the statin group and 8/73 (11.0%) participants receiving placebo, for a non-significant decrease in risk (RR 0.47, 95% CI 0.15 to 1.52). Several studies reported muscle enzyme levels as safety measures, but only three (with a total of 188 participants) reported explicitly on clinical muscle syndromes, with seven events reported and no significant difference found between statin users and controls (RR 0.94, 95% CI 0.24 to 3.63). The only participant-reported outcome was nausea in one small study,with no significant difference in risk between groups.Two studies compared different doses of atorvastatin, with a total of 145 participants, but reported data were not sufficient to allow us to determine the effect of higher doses on any outcome.. Evidence was insufficient to allow review authors to conclude that statin use resulted in either a reduction or an increase in any of the outcomes examined. The existing body of evidence leaves questions about the benefits of perioperative use of statins for vascular surgery unanswered. Widespread use of statins in the target population means that it may now be difficult for researchers to undertake the large RCTs needed to demonstrate any effect on the incidence of postoperative cardiovascular events. However, participant-reported outcomes have been neglected and warrant further study.

Topics: Adult; Angioplasty; Atherosclerosis; Atorvastatin; Cardiovascular Diseases; Cause of Death; Cholestyramine Resin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lovastatin; Perioperative Care; Postoperative Complications; Pyrroles; Randomized Controlled Trials as Topic; Sitosterols; Vascular Surgical Procedures

Plant sterols as ingredients to functional foods are recommended for lowering LDL cholesterol. However, there is an ongoing discussion whether the use of plant sterols is safe.. Genetic analyses showed that common variants of the ATP binding cassette transporter G8 (ABCG8) and ABO genes are associated with elevated circulating plant sterols and higher risk for cardiovascular disease. However, these data do not prove a causal role for plant sterols in atherosclerosis because the risk alleles in ABCG8 and ABO are also related to elevated total and LDL cholesterol levels. The ABO locus exhibits still further pleiotropy. Moreover, analyses in the general population indicated that moderately elevated circulating plant sterols are not correlated with present or future vascular disease. In agreement, novel studies using food frequency questionnaires, studies in experimental animals, and dietary intervention studies support that ingestion of plant sterols may be beneficial to cardiovascular health.. Taken together, current evidence supports the recommendations for the use of plant sterols as LDL cholesterol-lowering agents. Nevertheless, a prospective, randomized, controlled, double-blinded, intervention trial conclusively showing that plant sterol supplementation will prevent hard cardiovascular endpoints is not available to date.

Topics: Alleles; Animals; Anticholesteremic Agents; Atherosclerosis; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; ATP-Binding Cassette Transporters; Azetidines; Cholesterol, LDL; Ezetimibe; Genetic Loci; Humans; Lipoproteins; Phytosterols; Phytotherapy; Randomized Controlled Trials as Topic; Risk Factors; Sitosterols

Combination therapy may help high-risk patients achieve low-density lipoprotein cholesterol (LDL-C) goals. Impact of rosuvastatin 10 or 20 mg plus ezetimibe 10 mg (RSV10/EZE10 and RSV20/EZE10) has not been fully characterized previously. GRAVITY (NCT00525824) compared efficacy, safety and effect on biomarkers of RSV10/EZE10 and RSV20/EZE10 vs. simvastatin 40 mg and 80 mg plus EZE10 (SIM40/EZE10 and SIM80/EZE10) in patients with coronary heart disease (CHD) or CHD risk equivalent.. Adult patients (n = 833) were randomized to RSV10/EZE10, RSV20/EZE10, SIM40/EZE10 or SIM80/EZE10. Following a 6-week dietary lead-in, patients received 6 weeks' statin monotherapy followed by same statin dose plus ezetimibe for 6 more weeks. Primary endpoint was LDL-C change from baseline to 12 weeks.. Significantly greater (p < 0.05) reductions in LDL-C and other atherogenic lipids were observed with RSV20/EZE10 vs. SIM40/EZE10 and SIM80/EZE10 and with RSV10/EZE10 vs. SIM40/EZE10. A significantly greater proportion of patients achieved LDL-C goals of <100 mg/dl and <70 mg/dl with RSV20/EZE10 vs. SIM40/EZE10 and SIM80/EZE10 and with RSV10/EZE10 vs. SIM40/EZE10. LDL-C was reduced ∼10-14% further with combination therapy vs. monotherapy. Statin monotherapy reduced cholesterol and bile acid synthesis biomarkers, ezetimibe reduced β-sitosterol (sterol absorption marker), and combination therapy achieved additive reductions in lipoprotein-associated phospholipase A2 mass and activity, free cholesterol and 7-ketocholesterol. Safety profiles of rosuvastatin/ezetimibe and simvastatin/ezetimibe combinations were comparable.. Co-administration of rosuvastatin 10 or 20 mg plus ezetimibe achieved significant improvements in lipid profiles in high-risk patients vs. simvastatin 40 or 80 mg plus ezetimibe.

Topics: Absorption; Adult; Atherosclerosis; Azetidines; Biomarkers; Cholesterol, LDL; Coronary Disease; Drug Administration Schedule; Ezetimibe; Female; Fluorobenzenes; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Lipids; Lipoproteins; Male; Pyrimidines; Risk; Rosuvastatin Calcium; Simvastatin; Sitosterols; Sulfonamides; Treatment Outcome

The object of our study was to compare the effect of high-dose vs low-dose atorvastatin vs nonstatin-based treatment (cholestyramine plus sitosterol) on cell composition of carotid plaque.. We recruited 60 hypercholesterolemic patients (total cholesterol, 5.83-7.64 mmol/L) eligible for carotid endarterectomy. Three months before surgery, patients were randomized into 3 groups (n=20) receiving atorvastatin 10 mg/day (AT-10) or atorvastatin 80 mg/day (AT-80) or cholestyramine 8 g/day plus sitosterol 2.5 g/day. Analysis of cell composition was performed on endarterectomy specimens.. The 3 treatments resulted in a significant reduction of total cholesterol and low-density lipoprotein cholesterol (LDL-C), although the decrease in total cholesterol and LDL-C was of smaller magnitude in the cholestyramine plus sitosterol group. The 3 regimens did not influence the levels of inflammatory markers (including high-sensitivity C-reactive protein). Macrophage content was significantly lower in the AT-10 group plaques compared to the cholestyramine plus sitosterol group. It was further reduced in the AT-80 group plaques. These differences were no longer significant after adjustment for changes in LDL-C. No difference in lymphocyte number was observed among treatments, whereas the content of smooth muscle cells was higher in the AT- 80 group. An inverse association was observed between LDL-C changes in the 3 groups and macrophage content in the plaques.. Short-term treatment with high-dose statin is superior to a nonstatin lipid-lowering regimen in reducing the macrophage cell content within atherosclerotic lesions, but this effect was determined by the degree of LDL-C-lowering.

Topics: Aged; Aged, 80 and over; Anticholesteremic Agents; Atherosclerosis; Atorvastatin; Biomarkers; C-Reactive Protein; Cholesterol, LDL; Cholestyramine Resin; Endarterectomy, Carotid; Female; Heptanoic Acids; Humans; Hypercholesterolemia; Lymphocyte Count; Macrophages; Male; Pyrroles; Sitosterols

It is controversial whether atherosclerosis is linked to increased intestinal cholesterol absorption or synthesis in humans. The aim of the present study was to relate atherosclerosis to the measurements of plasma markers of cholesterol synthesis (desmosterol, lathosterol) and absorption (campesterol, sitosterol). In healthy male (n=344), non-obese, non-diabetics, belonging to the city of São Paulo branch of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), we measured in plasma these non-cholesterol sterol markers, together with their anthropometric, dietary parameters, traditional atherosclerotic risk factors, and blood chemistry, coronary arterial calcium score (CAC), and ultrasonographically measured common carotid artery intima-media thickness (CCA-IMT). Cases with CAC>zero had the following parameters higher than cases with CAC = zero: age, waist circumference (WC), plasma total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and non-high density lipoprotein-cholesterol (non HDL-C). Plasma desmosterol and campesterol, duly corrected for TC, age, body mass index (BMI), waist circumference (WC), hypertension, smoking, and the homeostasis model assessment-insulin resistance (HOMA-IR) correlated with CAC, but not with CCA-IMT. The latter related to increased age, BMI, waist circumference (WC), and systolic blood pressure (SBP). Plasma HDL-C concentrations did not define CAC or CCA-IMT degrees, although in relation to the lower tertile of HDL-C in plasma the higher tertile of HDL-C had lower HOMA-IR and concentration of a cholesterol synthesis marker (desmosterol). Present work indicated that increased cholesterol synthesis and absorption represent primary causes of CAD, but not of the common carotid artery atherosclerosis.

Topics: Adult; Aged; Atherosclerosis; Biomarkers; Body Mass Index; Brazil; Calcium; Carotid Artery, Common; Carotid Intima-Media Thickness; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Coronary Vessels; Cross-Sectional Studies; Desmosterol; Female; Humans; Intestinal Absorption; Intestinal Mucosa; Longitudinal Studies; Male; Middle Aged; Phytosterols; Prospective Studies; Sitosterols; Tomography, X-Ray Computed; Ultrasonography

Patients with cardiac sarcoidosis (CS) suffer from myocardial inflammation, but atherosclerosis is not infrequent in these patients. However, the classical atherosclerotic risk factors, such as perturbed serum lipids and whole-body cholesterol metabolism, remain unravelled in CS.. We assessed serum non-cholesterol sterols, biomarkers of whole-body cholesterol synthesis and cholesterol absorption efficiency, with gas-liquid chromatography in 39 patients with histologically verified CS and in an age-adjusted random population sample (n = 124).. CS was inactive or responding to treatment in all patients. Concentrations of serum, LDL, and HDL cholesterol and serum triglycerides were similar in CS patients and in control subjects. Cholesterol absorption markers were higher in CS patients than in controls (eg serum campesterol to cholesterol ratio in CS 246 ± 18 vs in controls 190 ± 8 10(2) x μmol/mmol of cholesterol, p = 0.001). Cholesterol synthesis markers were lower in CS patients than in controls (eg serum lathosterol to cholesterol ratio in CS 102 ± 8 vs in controls 195 ± 5 10(2) x μmol/mmol of cholesterol, p = 0.000). In CS patients, cholesterol absorption markers significantly correlated with plasma prohormone brain natriuretic peptide (proBNP), a marker of hemodynamic load.. High cholesterol absorption efficiency, which is suggested to be atherogenic, characterized the metabolic profile of cholesterol in CS patients. The association between cholesterol absorption efficiency and plasma proBNP concentration, which suggests a link between inflammation, cholesterol homeostasis, and hemodynamic load, warrants further studies in order to confirm this finding and to reveal the underlying mechanisms.

Topics: Adult; Aged; Atherosclerosis; Body Mass Index; Cardiomyopathies; Case-Control Studies; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diet; Down-Regulation; Female; Finland; Heart Diseases; Hemodynamics; Homeostasis; Humans; Inflammation; Lipoproteins; Male; Middle Aged; Phytosterols; Risk Factors; Sarcoidosis; Sitosterols

The aim of our study was to investigate vascular effects of oxysterols and oxyphytosterols on reactive oxygen species (ROS), endothelial progenitor cells, endothelial function and atherogenesis.. Male apoE-/-mice were treated with cholesterol, sitosterol, 7-ß-OH-cholesterol, 7-ß-OH-sitosterol, or cyclodextrin by daily intraperitoneal application. The respective concentrations in the plasma and in the arterial wall were determined by gas chromatography-flame ionization or mass spectrometry. ROS production was assessed by electron-spin resonance spectroscopy in the aorta, endothelial function of aortic rings and atherosclerosis in the aortic sinus was quantitated after 4 weeks.. Compared to vehicle, there was no difference in plasma cholesterol levels and arterial wall concentrations after i.p. application of cholesterol. 7-ß-OH-cholesterol concentrations were increased in the plasma (33.7±31.5 vs. 574.57.2±244.92 ng/ml) but not in the arterial wall (60.1±60.1 vs. 59.3±18.2 ng/mg). Sitosterol (3.39±0.96 vs. 8.16±4.11 mg/dL; 0.08±0.04 vs. 0.16±0.07 μg/mg, respectively) and 7-ß-OH-sitosterol concentrations (405.1±151.8 vs. 7497±3223 ng/ml; 0.24±0.13 vs. 16.82±11.58 ng/mg, respectively) increased in the plasma and in the aorta. The i.p-application of the non-oxidized cholesterol or sitosterol did not induce an increase of plasma oxysterols or oxyphytosterols concentrations. Oxidative stress in the aorta was increased in 7-ß-OH-sitosterol treated mice, but not in mice treated with cholesterol, sitosterol, or 7-ß-OH-cholesterol. Moreover, cholesterol, sitosterol, 7-ß-OH-cholesterol, and 7-ß-OH-sitosterol did not affect endothelial-dependent vasodilation, or early atherosclerosis.. Increased oxyphytosterol concentrations in plasma and arterial wall were associated with increased ROS production in aortic tissue, but did not affect endothelial progenitor cells, endothelial function, or early atherosclerosis.

Topics: Animals; Aorta; Aortic Diseases; Apolipoproteins E; Atherosclerosis; Cell Movement; Cells, Cultured; Cholesterol; Cyclodextrins; Disease Models, Animal; Endothelial Progenitor Cells; Hydroxycholesterols; Male; Mice, Inbred C57BL; Mice, Knockout; Oxidative Stress; Reactive Oxygen Species; Sitosterols; Time Factors; Vasodilation

Cholesterol analogs have been used to treat hypercholesterolemia. The present study was to examine the effect of dihydrocholesterol (DC) on plasma total cholesterol (TC) compared with that of β-sitosterol (SI) in hamsters fed a high cholesterol diet.. Forty-five male hamsters were randomly divided into 6 groups, fed either a non-cholesterol diet (NCD) or one of five high-cholesterol diets without addition of DC and SI (HCD) or with addition of 0.2% DC (DA), 0.3% DC (DB), 0.2% SI (SA), and 0.3% SI (SB), respectively, for 6 weeks. Results showed that DC added into diet at a dose of 0.2% could reduce plasma TC by 21%, comparable to that of SI (19%). At a higher dose of 0.3%, DC reduced plasma TC by 15%, less effective than SI (32%). Both DC and SI could increase the excretion of fecal sterols, however, DC was more effective in increasing the excretion of neutral sterols but it was less effective in increasing the excretion of acidic sterols compared with SI. Results on the incorporation of sterols in micellar solutions clearly demonstrated both DC and SI could displace the cholesterol from micelles with the former being more effective than the latter.. DC was equally effective in reducing plasma cholesterol as SI at a low dose. Plasma TC-lowering activity of DC was mediated by inhibiting the cholesterol absorption and increasing the fecal sterol excretion.

Topics: Adipose Tissue; Animal Feed; Animals; Anticholesteremic Agents; Aortic Diseases; Atherosclerosis; Bile Acids and Salts; Cholestanol; Cholesterol; Cholesterol, Dietary; Cricetinae; Drug Evaluation, Preclinical; Feces; Gene Expression Profiling; Hyperlipoproteinemia Type II; Intestinal Absorption; Lipids; Lipoproteins; Liver; Male; Mesocricetus; Metabolic Networks and Pathways; Micelles; Molecular Structure; Organ Size; Plaque, Atherosclerotic; Random Allocation; RNA, Messenger; Sitosterols; Sterols; Viscera

Atherosclerosis is a chronic inflammatory disease, which is associated with increased expression of adhesion molecules and monocyte recruitment into the arterial wall. This study evaluated whether hexane extracts from the edible part (DB-H1) or bark region (DB-H2) of Dioscorea. batatas Decne have anti-atherosclerotic properties in vivo and in vitro experiments. We also identified bioactive components in the hexane extracts. Thirty-six apolipoprotein E (ApoE(-/-) ) mice and 12 control (C57BL/6J) mice were given a Western-type diet for 11 or 21 wk. To examine the effects of yam extracts on lesion development, ApoE(-/-) mice were orally administered DB-H1 or DB-H2 for the duration of the study (200 mg/kg b.w./day, 3 times per wk). Both DB-H1 and DB-H2 significantly reduced the total atherosclerotic lesion area in the aortic root. In addition, plasma concentrations of total cholesterol, oxidized-low-density lipoprotein, and c-reactive protein were decreased by administration of DB-H1 and DB-H2. Consistent with the in vivo observations, DB-H1 and DB-H2 inhibited tumor necrosis factor (TNF)-α-induced vascular cell adhesion molecule-1 expression and adhesion of THP-1 monocytes to TNF-α-activated vascular smooth muscle cells. It was also found that treatment with DB-H1 or DB-H2 resulted in the inhibition nitric oxide (NO) and reactive oxygen species production and iNOS expression in macrophages. Thus, DB-H1 and DB-H2 seem to influence atherosclerosis by affecting the production of inflammatory mediators in vivo. Our results suggest that yam extracts have the potential to be used in the prevention of atherosclerosis.

Topics: Animals; Aorta; Apolipoproteins E; Atherosclerosis; C-Reactive Protein; Cardiovascular Agents; Dioscorea; In Vitro Techniques; Inflammation Mediators; Linoleic Acids; Lipoproteins, LDL; Macrophages; Male; Mice; Mice, Inbred C57BL; Monocytes; Muscle, Smooth, Vascular; Phytotherapy; Plant Extracts; Reactive Oxygen Species; Sitosterols; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

Euterpe Oleracea (açai) is a fruit from the Amazon region whose chemical composition may be beneficial for individuals with atherosclerosis. We hypothesized that consumption of Euterpe Oleracea would reduce atherosclerosis development by decreasing cholesterol absorption and synthesis.. Male New Zealand rabbits were fed a cholesterol-enriched diet (0.5%) for 12 weeks, when they were randomized to receive Euterpe Oleracea extract (n = 15) or water (n = 12) plus a 0.05% cholesterol-enriched diet for an additional 12 weeks. Plasma phytosterols and desmosterol were determined by ultra-performance liquid chromatography and mass spectrometry. Atherosclerotic lesions were estimated by computerized planimetry and histomorphometry.. At sacrifice, animals treated with Euterpe Oleracea had lower levels of total cholesterol (p =0.03), non-HDL-cholesterol (p = 0.03) and triglycerides (p = 0.02) than controls. These animals had smaller atherosclerotic plaque area in their aortas (p = 0.001) and a smaller intima/media ratio (p = 0.002) than controls, without differences in plaque composition. At the end of the study, campesterol, β-sitosterol, and desmosterol plasma levels did not differ between groups; however, animals treated with Euterpe Oleracea showed lower desmosterol/campesterol (p = 0.026) and desmosterol/ β-sitosterol (p =0.006) ratios than controls.. Consumption of Euterpe Oleracea extract markedly improved the lipid profile and attenuated atherosclerosis. These effects were related in part to a better balance in the synthesis and absorption of sterols.

Topics: Animals; Arecaceae; Atherosclerosis; Cholesterol; Cholesterol, Dietary; Chromatography, High Pressure Liquid; Desmosterol; Immunoenzyme Techniques; Lipids; Male; Phytosterols; Phytotherapy; Plant Extracts; Rabbits; Sitosterols; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Plant sterols such as sitosterol and campesterol are frequently applied as functional food in the prevention of atherosclerosis. Recently, it became clear that plasma derived plant sterols accumulate in murine brains. We questioned whether plant sterols in the brain are associated with alterations in brain cholesterol homeostasis and subsequently with brain functions. ATP binding cassette (Abc)g5-/- mice, a phytosterolemia model, were compared to Abcg5+/+ mice for serum and brain plant sterol accumulation and behavioral and cognitive performance. Serum and brain plant sterol concentrations were respectively 35-70-fold and 5-12-fold increased in Abcg5-/- mice (P<0.001). Plant sterol accumulation resulted in decreased levels of desmosterol (P<0.01) and 24(S)-hydroxycholesterol (P<0.01) in the hippocampus, the brain region important for learning and memory functions, and increased lanosterol levels (P<0.01) in the cortex. However, Abcg5-/- and Abcg5+/+ displayed no differences in memory functions or in anxiety and mood related behavior. The swimming speed of the Abcg5-/- mice was slightly higher compared to Abcg5+/+ mice (P<0.001). In conclusion, plant sterols in the brains of Abcg5-/- mice did have consequences for brain cholesterol metabolism, but did not lead to an overt phenotype of memory or anxiety related behavior. Thus, our data provide no contra-indication for nutritional intake of plant sterol enriched nutrition.

Topics: Affect; Animals; Anxiety Disorders; Atherosclerosis; ATP-Binding Cassette Transporters; Behavior, Animal; Brain; Cholesterol; Desmosterol; Diet; Hippocampus; Homeostasis; Hydroxycholesterols; Hypercholesterolemia; Intestinal Diseases; Lanosterol; Lipid Metabolism, Inborn Errors; Male; Maze Learning; Memory; Mice; Mice, Mutant Strains; Phytosterols; Sitosterols; Stigmasterol

Abnormal proliferation of vascular smooth muscle cells (VSMCs) plays a central role in the pathogenesis of atherosclerosis. β-Sitosterol, an important phytosterol found in plant food, is known to exert antiatherosclerosis activity. However, the molecular mechanisms underlying β-sitosterol-induced antiproliferation of VSMCs were still not clear. This study demonstrated that β-sitosterol (1-20 μM) concentration-dependently inhibited proliferation of rat aortic smooth muscle cells (RASMCs) without cytotoxic effect. Flow cytometric analysis revealed that β-sitosterol arrested cell cycle progression through down-regulation of cyclin E and cyclin-dependent kinase (CDK)2 and up-regulation of p21cip1. In the β-sitosterol-treated RASMCs, the formation of the CDK2-p21cip1 complex was increased and the assayable CDK2 activity was decreased. Knockdown of the expression of p21cip1 gene prevented β-sitosterol-induced cell cycle arrest in RASMCs. In conclusion, β-sitosterol inhibited VSMC proliferation by increasing the levels of p21cip1 protein, which in turn inhibited the CDK2 activity, and finally interrupted the progress of the cell cycle.

Topics: Animals; Aorta, Thoracic; Atherosclerosis; Cell Cycle; Cell Proliferation; Cells, Cultured; Cyclin-Dependent Kinase Inhibitor p21; Hypolipidemic Agents; Male; Muscle, Smooth, Vascular; Rats; Rats, Sprague-Dawley; Sitosterols; Up-Regulation

Oxidation of LDL is hypothesised as an early and critical event in atherogenesis. Oxidised LDL (oxLDL) favour the transformation of macrophages into foam cells, an important cell involved in atherosclerosis. Furthermore, oxLDL cause multiple changes in macrophage functions. Thus, oxLDL induces certain genes, suppresses others and alters cell lipid metabolism. Consumption of a Mediterranean diet is associated with a low incidence of atherosclerotic disease, but data about the specific dietary constituents involved and mechanisms conferring cardioprotection are still sparse. The aim of the present study was to determine the effect of representative minor components of wine and olive oil on reactive oxygen species and eicosanoid synthesis induced by oxLDL-stimulated macrophages. We observed that exposure to non-toxic oxLDL concentrations leads to the production of H2O2 by RAW 264.7 macrophages and this effect was reverted by apocynin, a NADPH oxidase inhibitor. Moreover, oxLDL induced arachidonic acid (AA) release, cyclo-oxygenase-2 overexpression and subsequent PGE2 release. We observed that resveratrol and tyrosol revert H2O2 production induced by oxLDL as well as AA release and PGE2 synthesis and that these effects were not as a consequence of these compounds interfering with the oxLDL binding to their receptors. Interestingly, beta-sitosterol presence enhances these polyphenol actions. Thus, we found a synergistic action of polyphenols of olive oil and wine and beta-sitosterol of olive oil led to the modulation of the effects of oxLDL on oxidative stress and PGE2 synthesis.

Topics: Animals; Antioxidants; Arachidonic Acid; Atherosclerosis; Cells, Cultured; Dinoprostone; Hydrogen Peroxide; Lipid Metabolism; Lipoproteins, LDL; Macrophages; Mice; Olive Oil; Oxidative Stress; Phenylethyl Alcohol; Plant Oils; Protein Binding; Resveratrol; Sitosterols; Stilbenes; Wine

The cytoprotective effects of various solvent extracts of Artocarpus altilis (Parkinson) Fosberg were evaluated. The cytoprotective effects were determined in human U937 cells incubated with oxidized LDL (OxLDL) using the 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1, 3-benzene disulfonate (WST-1) assay. The results demonstrated that the ethyl acetate extract showed cytoprotective activities. To identify the main cytoprotective components, a bioassay guided isolation of the ethyl acetate extract afforded b-sitosterol (1) and six flavonoids (2-7). Their chemical structures were established on the basis of spectroscopic evidence and comparison with literature data. Of these compounds, compound 6 was obtained from A. altilis for the first time. The cytoprotective effect offers good prospects for the medicinal applications of A. altilis.

Topics: Artocarpus; Atherosclerosis; Biological Assay; Cell Survival; Flavonoids; Humans; Lipoproteins, LDL; Plant Extracts; Plant Leaves; Sitosterols; U937 Cells

Several studies in humans have demonstrated the hypocholesterolemic effect of plant sterol consumption. It is unclear whether plant sterols regulate lipoprotein metabolism in the liver and intestines, thereby decreasing the levels of circulating atherogenic lipoproteins. We investigated the effect of the three main phytosterols: stigmasterol, campesterol, and beta-sitosterol on lipoprotein production in HepG2 human liver cells and Caco2 human intestinal cells and the mechanisms involved. Cells were incubated for 24h with 50 micromol/L of the different phytosterols or 10 micromol/L of atorvastatin. Very low-density lipoprotein levels (measured by apolipoprotein (apo) B100) in HepG2 cells and chylomicron levels (measured by apoB48) in Caco2 cells were measured using western blotting. Intracellular cholesterol levels were measured using gas chromatography. Analysis was carried out using Student's t-test and ANOVA. Secretion levels of apoB100 significantly decreased by approximately 30% after incubation with all phytosterols compared to control. In addition, cholesterol ester (CE) concentrations significantly decreased when HepG2 cells were incubated with the phytosterols compared to control cells. Secretion of apoB48 from intestinal cells significantly decreased by 15% with stigmasterol, 16% with campesterol and 19% beta-sitosterol compared to control. Collectively the data suggests that plant sterols limit lipid (CE) availability in cells. Decreases in circulating levels of LDL and chylomicron remnants seen in humans with the consumption of margarine phytosterols are possibly due to their effect on lipid production in cells and would therefore reduce the risk of developing cardiovascular disease.

Topics: Anticholesteremic Agents; Apolipoprotein B-100; Apolipoprotein B-48; Apolipoproteins B; Atherosclerosis; Atorvastatin; Caco-2 Cells; Carcinoma, Hepatocellular; Cholesterol; Drug Synergism; Enterocytes; Hepatocytes; Heptanoic Acids; Humans; Liver Neoplasms; Margarine; Phytosterols; Pyrroles; Sitosterols; Stigmasterol

Topics: Animals; Arachidonic Acid; Atherosclerosis; Rabbits; Safflower Oil; Sitosterols; Sterols

Topics: Arteriosclerosis; Atherosclerosis; Diet; Sitosterols; Steroids

Topics: Arachidonic Acid; Arteriosclerosis; Atherosclerosis; Cholesterol; Humans; Hypercholesterolemia; Safflower Oil; Sitosterols; Steroids

Topics: Animals; Arteriosclerosis; Atherosclerosis; Cholestanol; Cholesterol; Rabbits; Sitosterols; Steroids

Topics: Animals; Arteriosclerosis; Atherosclerosis; Cholesterol; Rabbits; Sitosterols; Steroids