Plasma Cholesterol-lowering Effect Research Articles

Polyphenols, Saponins and Phytosterols in Lentils and Their Health Benefits: An Overview.

The lentil (Lens culinaris L.) is one of the most important legumes (family, Fabaceae). It is a natural functional food rich in many bioactive compounds, such as polyphenols, saponins and phytosterols. Several studies have demonstrated that the consumption of lentils is potentially important in reducing the incidence of a number of chronic diseases, due to their bioactive compounds. The most common polyphenols in lentils include phenolic acids, flavan-3-ol, flavonols, anthocyanidins, proanthocyanidins or condensed tannins, and anthocyanins, which play an important role in the prevention of several degenerative diseases in humans, due to their antioxidant activity. Furthermore, lentil polyphenols are reported to have antidiabetic, cardioprotective and anticancer activities. Lentil saponins are triterpene glycosides, mainly soyasaponins I and βg. These saponins have a plasma cholesterol-lowering effect in humans and are important in reducing the risk of many chronic diseases. Moreover, high levels of phytosterols have been reported in lentils, especially in the seed coat, and β-sitosterol, campesterol, and stigmasterol are the most abundant. Beyond their hypocholesterolemic effect, phytosterols in lentils are known for their anti-inflammatory activity. In this review, the current information on the nutritional composition, bioactive compounds including polyphenols, saponins and phytosterols, and their associated health-promoting effects are discussed.

Diosgenin and Its Analogs: Potential Protective Agents Against Atherosclerosis.

Atherosclerosis is a chronic inflammatory disease of the artery wall associated with lipid metabolism imbalance and maladaptive immune response, which mediates most cardiovascular events. First-line drugs such as statins and antiplatelet drug aspirin have shown good effects against atherosclerosis but may lead to certain side effects. Thus, the development of new, safer, and less toxic agents for atherosclerosis is urgently needed. Diosgenin and its analogs have gained importance for their efficacy against life-threatening diseases, including cardiovascular, endocrine, nervous system diseases, and cancer. Diosgenin and its analogs are widely found in the rhizomes of Dioscore, Solanum, and other species and share similar chemical structures and pharmacological effects. Recent data suggested diosgenin plays an anti-atherosclerosis role through its anti-inflammatory, antioxidant, plasma cholesterol-lowering, anti-proliferation, and anti-thrombotic effects. However, a review of the effects of diosgenin and its natural structure analogs on AS is still lacking. This review summarizes the effects of diosgenin and its analogs on vascular endothelial dysfunction, vascular smooth muscle cell (VSMC) proliferation, migration and calcification, lipid metabolism, and inflammation, and provides a new overview of its anti-atherosclerosis mechanism. Besides, the structures, sources, safety, pharmacokinetic characteristics, and biological availability are introduced to reveal the limitations and challenges of current studies, hoping to provide a theoretical basis for the clinical application of diosgenin and its analogs and provide a new idea for developing new agents for atherosclerosis.

Cholesterol Absorption and Synthesis in Vegetarians and Omnivores

Vegetarian diets are considered health-promoting; however, a plasma cholesterol lowering effect is not always observed. We investigate the link between vegetarian-diet-induced alterations in cholesterol metabolism. We study male and female omnivores, lacto-ovo vegetarians, lacto vegetarians, and vegans. Cholesterol intake, absorption, and fecal sterol excretion are measured as well as plasma concentrations of cholesterol and noncholesterol sterols. These serve as markers for cholesterol absorption, synthesis, and catabolism. The biliary cholesterol secretion rate is estimated. Flux data are related to body weight. Individual vegetarian diet groups are statistically compared to the omnivore group. Lacto vegetarians absorb 44% less dietary cholesterol, synthesized 22% more cholesterol, and show no differences in plasma total and LDL cholesterol. Vegan subjects absorb 90% less dietary cholesterol, synthesized 35% more cholesterol, and have a similar plasma total cholesterol, but a 13% lower plasma LDL cholesterol. No diet-related differences in biliary cholesterol secretion and absorption are observed. Total cholesterol absorption is lower only in vegans. Total cholesterol input is similar under all vegetarian diets. Unaltered biliary cholesterol secretion and higher cholesterol synthesis blunt the lowered dietary cholesterol intake in vegetarians. LDL cholesterol is significantly lower only in vegans.

Whole Grain Rye Intake, Reflected by a Biomarker, Is Associated with Favorable Blood Lipid Outcomes in Subjects with the Metabolic Syndrome – A Randomized Study

Background and AimFew studies have explored the possible plasma cholesterol lowering effects of rye consumption. The aim of this secondary analysis in the SYSDIET study was to investigate the association between plasma alkylresorcinols (AR), a biomarker for whole grain wheat and rye intake, and blood lipid concentrations in a population with metabolic syndrome. Furthermore, we analyzed the associations between the AR C17∶0/C21∶0 ratio, a suggested marker of the relative intake of whole grain/bran rye, and blood lipid concentrations.MethodsParticipants were 30–65 years of age, with body mass index (BMI) 27–40 kg/m2 and had metabolic syndrome. Individuals were recruited through six centers in the Nordic countries and randomized either to a healthy Nordic diet (ND, n = 93), rich in whole grain rye and wheat, as well as berries, fruits and vegetables, rapeseed oil, three fish meals per week and low-fat dairy products, or a control diet (n = 65) for 18/24 weeks. Associations between total plasma AR concentration and C17∶0/C21∶0 homologue ratio and blood lipids were investigated in pooled (ND + control group) regression analyses at 18/24 weeks adjusted for baseline value for the dependent variable, age, BMI and statin use.ResultsWhen adjusted for confounders, total plasma AR at 18/24 weeks was not significantly associated with blood lipids but the AR ratio C17∶0/C21∶0 was inversely associated with LDL cholesterol concentrations (B (95% CI): −0.41 (−0.80 to −0.02)), log LDL/HDL cholesterol ratio (−0.20 (−0.37 to −0.03)), log non-HDL cholesterol (−0.20 (−0.37 to −0.03)), log apolipoprotein B (−0.12 (−0.24 to 0.00)) and log triglyceride concentrations (−0.35 (−0.59 to −0.12)).DiscussionIncreased proportion of whole grain rye, reflected by a biomarker, in the diet is associated with favorable blood lipid outcomes, a relationship that should be further investigated.Trial RegistrationClinicalTrials.gov NCT00992641

GW24-e2397 Rosuvastatin could modulate insulin signalling and inhibit atherosclerosis beyond its plasma cholesterol-lowering effect in insulin-resistant mice

ObjectivesTo provide evidence that rosuvastatin could improve insulin-resistance and inhibit atherogenesis by modulating insulin signalling, and whether this effect beyond its plasma cholesterol-lowering effect.MethodsThirty-two 6-week-old low-density lipoprotein receptor deficient (LDLR-...

Inhibition of ileal apical but not basolateral bile acid transport reduces atherosclerosis in apoE−/− mice

ObjectiveInterruption of the enterohepatic circulation of bile acids induces hepatic bile acid synthesis, increases hepatic cholesterol demand, and increases clearance of apoB-containing lipoproteins in plasma. Based on these effects, bile acid sequestrants have been used for many years to treat hypercholesterolemia and the associated atherosclerosis. The objective of this study was to determine the effect of blocking ileal apical versus basolateral membrane bile acid transport on the development of hypercholesterolemia and atherosclerosis in mouse models. Methods and resultsApoE−/− and Ldlr−/− mice deficient in the apical sodium-dependent bile acid transporter (Asbt) or apoE−/− mice deficient in the basolateral bile acid transporter (Ostα) were fed an atherogenic diet for 16 weeks. Bile acid metabolism, cholesterol metabolism, gene expression, and development of atherosclerosis were examined. Mice deficient in Asbt exhibited the classic response to interruption of the enterohepatic circulation of bile acids, including significant reductions in hepatic and plasma cholesterol levels, and reduced aortic cholesteryl ester content. Ileal Fibroblast Growth Factor-15 (FGF15) expression was significantly reduced in Asbt−/−apoE−/− mice and was inversely correlated with expression of hepatic cholesterol 7-hydroxylase (Cyp7a1). Ileal FGF15 expression was directly correlated with plasma cholesterol levels and aortic cholesterol content. In contrast, plasma and hepatic cholesterol levels and atherosclerosis development were not reduced in apoE−/− mice deficient in Ostα. ConclusionsDecreases in ileal FGF15, with subsequent increases in hepatic Cyp7a1 expression and bile acid synthesis appear to be necessary for the plasma cholesterol-lowering and atheroprotective effects associated with blocking intestinal bile acid absorption.

Effect of Dietary Maitake (Grifola frondosa) Mushrooms on Plasma Cholesterol and Hepatic Gene Expression in Cholesterol-Fed Mice

To investigate the effects of dietary Grifola frondosa on cholesterol, normal mice were fed a diet containing 1% cholesterol (HC group) or 1% cholesterol and 10% freeze-dried G. frondosa powder (HC+G group) for 4 weeks and hepatic and plasma lipid levels were compared with those of a cholesterol-free diet-fed mice (N group). Hepatic total cholesterol (TC), triacylglycerol contents were considerably increased and plasma TC / phospholipid (PL) was also increased significantly in the HC group compared with the N group. However, plasma TC content decreased in the HC+G group compared with the HC group. To characterize the mechanisms responsible for lowered plasma cholesterol in G. frondosa-supplemented mice, hepatic gene expression was profiled using DNA microarray and gene ontology. Genome analyses revealed that de novo cholesterol synthesis genes were suppressed following cholesterol intake. However, expression of bile acid biosynthesis and low-density lipoprotein receptor genes showed little change. Scarb1, Abcg5, and Abcg8, involved in cholesterol transport and excretion, were slightly upregulated in the HC+G group compared with the HC group. These data indicate the plasma cholesterol-lowering effect of G. frondosa. Moreover, fatty acid (FA) β-oxidation was promoted via adipocytokine signaling pathways, and Saa, encodes serum amyloid A related to arteriosclerosis, was suppressed in the HC+G group.

341 Cholesterol Biosynthesis in Preterm Infants on Parenteral Nutrition with a Lipid Emulsion Containing 10% Fish Oil (FO): a Pilot Study

Background and AimsLimited data are available on the metabolic effects of intravenous fish oil (FO) in premature infant. We reported on the plasma cholesterol lowering effect of an intravenous lipid...

Rosuvastatin may Modulate Insulin Signaling and Inhibit Atherogenesis Beyond its Plasma Cholesterol-Lowering Effect in Insulin-Resistant Mice

To provide evidence that rosuvastatin may improve insulin-resistance and inhibit atherogenesis by modulating insulin signaling, and whether this effect occurs beyond its plasma cholesterol-lowering effect. Thirty-two 6-week-old low-density lipoprotein receptor deficient mice were randomized into 4 groups (n = 8 in each group): Normal control group (NC); High fat and high fructose diet group (HFF); HFF plus rosuvastatin group (HFFR); HFFR plus mevalonic acid group (HFFRMA). After 12 weeks, we measured fasting blood sugar, fasting insulin and cholesterol levels; the morphological concentrations of the aorta and aortic sinus; the expression of insulin receptor substrate 2, phosphorylated insulin receptor substrate 2, protein kinase B, phosphorylated protein kinase B and the glucose transporter 4 in the liver. Compared with other groups, fasting blood sugar and fasting insulin increased significantly in HFF group. Furthermore, HFF group had an increase in the morphological concentrations of the aorta and aortic sinus, but there was a significant decrease in the HFFRMA group and the HFFR group. Moreover, there was a high expression of insulin receptor substrate 2, phosphorylated insulin receptor substrate 2, protein kinase B, phosphorylated protein kinase B and the glucose transporter 4 in the HFFRMA and HFFR groups, but a low expression in the HFF group. No significant differences regarding each afore-mentioned index was observed in the HFFR and HFFRMA groups. Our data show that rosuvastatin may improve insulin-resistance and inhibit atherogenesis in HFF-fed mice by partially reversing the decrease in the insulin stimulated insulin receptor substrate 2/Phosphatidylinositol 3-kinase/protein kinase B/glucose transporter 4 pathway in the liver, and that this effect is independent of its cholesterol-lowering effect.

Addition of Methionine to Rice Protein Affects Hepatic Cholesterol Output Inducing Hypocholesterolemia in Rats Fed Cholesterol-Free Diets

To elucidate whether a low methionine (Met)/glycine (Gly) ratio is responsible for the hypocholesterolemic effect of rice protein (RP), the effects of adding Met to RP, increasing its Met/Gly ratio, on hepatic cholesterol output was investigated in rats fed cholesterol-free diets. The hepatic secretion of cholesterol into bile or circulation was measured from isolated perfused livers of 7-week-old male Wistar rats fed RP (cultivar Koshihikari) with a lower Met/Gly ratio and methionine-supplemented RP with a higher Met/Gly ratio (RP-M) matched with casein (CAS). RP-M produced a significant hypocholesterolemic effect, whereas the effect of RP on plasma cholesterol level was comparable to that of CAS. Hepatic accumulation of total lipids, cholesterol, and phospholipids was higher in RP-M rats than in RP rats, again following a pattern similar to that in CAS rats. The hepatic total and very-low-density lipoprotein (VLDL)-cholesterol secretions into circulation were effectively decreased by RP, but not by RP-M. Bile flow and biliary outputs of bile acids, cholesterol, and phospholipids were significantly stimulated by RP-M, causing an increase in fecal sterol excretion compared with CAS and RP. Neither biliary output nor fecal excretion of bile acids was affected by RP compared with CAS. The present results demonstrate that the plasma cholesterol-lowering effect of RP cannot be merely ascribed to the low Met/Gly ratio of RP in growing rats fed cholesterol-free diets. Results suggest that the hypocholesterolemic response induced by RP-M with a higher Met/Gly ratio primarily contributes to the stimulation of hepatic cholesterol for elimination via biliary secretion rather than the inhibition of hepatic cholesterol release via VLDL into circulation.

Raw Chinese Yam (Dioscorea opposita) Promotes Cecal Fermentation and Reduces Plasma Non-HDL Cholesterol Concentration in Rats

We examined the effects of raw Chinese yam (Dioscorea opposita), containing resistant starch (RS), on lipid metabolism and cecal fermentation in rats. Raw yam (RY) and boiled yam (BY) contained 33.9% and 6.9% RS, respectively. Male Sprague-Dawley rats were fed a cholesterol-free, control (C) diet supplemented with or without 15 and 30 g of RY or BY/100 g for 3 wk. Plasma total cholesterol concentrations in the tail vein of rats fed the 30% RY diet were significantly lower than in the C group throughout the feeding period. Compared with the C group, non-HDL concentrations in arterial plasma in the 30% RY group was significantly reduced. Liver cholesterol concentration in rats fed the 30% RY diet was significantly higher compared with those fed the C diet. Hepatic cholesterol 7α-hydroxylase mRNA and fecal bile acid excretion were significantly higher in the BY, but not the RY group, compared with the C group. Fecal cholesterol excretion in the 30% RY group was greater compared with the C group. Hepatic microsomal triacylglycerol transfer protein mRNA was significantly lower in the 30% RY group compared with the C group. Cecal pools of acetate, propionate and butyrate were 113-257%, 181-476% and 410-789% greater in the RY group compared with the C group. These results suggest raw yam is effective as a source of RS and facilitates production of short chain fatty acid (SCFA), especially butyrate, in the rat cecum. In addition, RY has a plasma-cholesterol lowering effect, possibly due to the inhibited release of VLDL.

A Randomized Double-Blind, Placebo-Controlled Study to Establish the Effects of Spirulina in Elderly Koreans

Aims: This study was conducted to determine the antioxidant capacity, immunomodulatory and lipid-lowering effects of spirulina in healthy elderly subjects and to document the effectiveness of spirulina as a functional food for the elderly. Methods: A randomized double-blind, placebo-controlled study was performed. The subjects were 78 individuals aged 60–87 years and were randomly assigned in a blinded fashion to receive either spirulina or placebo. The elderly were instructed to consume the spirulina or placebo at home, 8 g/day, for 16 consecutive weeks. Results: In male subjects, a significant plasma cholesterol-lowering effect was observed after the spirulina intervention (p < 0.05). Spirulina supplementation resulted in a significant rise in plasma interleukin (IL)-2 concentration, and a significant reduction in IL-6 concentration. A significant time-by-treatment intervention for total antioxidant status was observed between spirulina and placebo groups (p < 0.05). In female subjects, significant increases in IL-2 level and superoxide dismutase activity were observed (p < 0.05) after spirulina supplementation. There were significant reductions in total cholesterol in female subjects. Conclusions: The results demonstrate that spirulina has favorable effects on lipid profiles, immune variables, and antioxidant capacity in healthy, elderly male and female subjects and is suitable as a functional food.

3-(4′-Hydroxyl-3′,5′-dimethoxyphenyl)propionic Acid, an Active Principle of Kimchi, Inhibits Development of Atherosclerosis in Rabbits

The effects of 3-(4'-hydroxyl-3',5'-dimethoxyphenyl)propionic acid (HDMPPA) originating from Korean cabbage kimchi were investigated, showing an antioxidant effect on the prevention of atherosclerosis in hypercholesterolemic rabbits. Twenty-one 3-month-old rabbits were fed an atherogenic diet containing 0.5% (w/w) cholesterol and 10% (w/w) coconut oil, whereas another two groups were given an atherogenic diet with intravenous injection of either HDMPPA or simvastatin (0.33 mg/kg/day) for 4 weeks. HDMPPA inhibited the oxidative modification of low-density lipoprotein (IC 50 = 1.4 microg/mL) and increased 2,2'-diphenyl-1-picrylhydrazyl radical scavenging activity (IC 50 = 0.78 microg/mL) in a dose-dependent manner. In hypercholesterolemic rabbits, the thickness of intima of aorta of the HDMPPA group was significantly reduced (control versus HDMPPA, 42%; simvastatin, 38%) without a plasma cholesterol-lowering effect. Thiobarbituric acid reactive substance formation in the plasma of the HDMPPA group was significantly decreased compared to that of the control group. Furthermore, the generation of vascular reactive oxygen species in HDMPPA group was suppressed as the cyclooxygenase-2 protein level decreased. These findings suggest that HDMPPA prevents the development of aortic atherosclerosis in high-cholesterol-fed rabbits. The antiatherosclerotic effect of HDMPPA may be due to an antioxidative effect at a low dose without cholesterol-lowering effects.

乳酸発酵させたオカラ豆乳のラット血漿コレステロール低下作用

近年増加傾向にある高脂血症の予防食品として，血中コレステロール値低下作用が認められている豆乳とオカラを乳酸発酵させた食品「発酵オカラ豆乳」を作製した．当該食品の有効性を検討するため，豆乳，発酵豆乳，発酵オカラ豆乳で各々20％置換した飼料を高コレステロール食投与ラットに投与し血中および肝臓脂質濃度に及ぼす影響を調べた．血中総コレステロール濃度は豆乳，発酵豆乳投与群で対照群と比較して低下し，さらに発酵オカラ豆乳群では有意に連続的に低値を示した．肝臓コレステロール濃度はいずれの試験群も対照群と比較して有意に低値であった．また，豆乳投与群と発酵オカラ豆乳投与群で，肝臓トリグリセリドの蓄積抑制効果が認められた．以上より，豆乳の一部をオカラで代替した発酵オカラ豆乳は産業廃棄物オカラの有効利用という利点を持ち，かつ，オカラを含むことにより発酵豆乳よりも血中コレステロール濃度低下作用，肝臓トリグリセリド蓄積低下作用が促進することが認められ，高脂血症予防のための機能性食品として利用可能である．

Structural and Functional Variations in Human Apolipoprotein E3 and E4

There are three major apolipoprotein E (apoE) isoforms. Although APOE-epsilon3 is considered a longevity gene, APOE-epsilon4 is a dual risk factor to atherosclerosis and Alzheimer disease. We have expressed full-length and N- and C-terminal truncated apoE3 and apoE4 tailored to eliminate helix and domain interactions to unveil structural and functional disturbances. The N-terminal truncated apoE4-(72-299) and C-terminal truncated apoE4-(1-231) showed more complicated or aggregated species than those of the corresponding apoE3 counterparts. This isoformic structural variation did not exist in the presence of dihexanoylphosphatidylcholine. The C-terminal truncated apoE-(1-191) and apoE-(1-231) proteins greatly lost lipid binding ability as illustrated by the dimyristoylphosphatidylcholine turbidity clearance. The low density lipoprotein (LDL) receptor binding ability, determined by a competition binding assay of 3H-LDL to the LDL receptor of HepG2 cells, showed that apoE4 proteins with N-terminal (apoE4-(72-299)), C-terminal (apoE4-(1-231)), or complete C-terminal truncation (apoE4-(1-191)) maintained greater receptor binding abilities than their apoE3 counterparts. The cholesterol-lowering abilities of apoE3-(72-299) and apoE3-(1-231) in apoE-deficient mice were decreased significantly. The structural preference of apoE4 to remain functional in solution may explain the enhanced opportunity of apoE4 isoform to display its pathophysiologic functions in atherosclerosis and Alzheimer disease.

ACAT inhibitor pactimibe sulfate (CS-505) reduces and stabilizes atherosclerotic lesions by cholesterol-lowering and direct effects in apolipoprotein E-deficient mice

The objective of the present study was to determine whether a novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, pactimibe sulfate (CS-505), could reduce atherosclerotic lesions beyond and independent of the reduction achieved by cholesterol lowering alone from two different types of lesions. (1) Early lesion model. Twelve-week-old apolipoprotein E (apoE) −/− mice were treated with 0.03 or 0.1% (w/w) CS-505, 0.1 or 0.3% avasimibe (CI-1011), or 3% cholestyramine for 12 weeks. Each treatment significantly reduced plasma cholesterol by a similar degree (43–48%). The antiatherosclerotic activity of 0.1% CS-505, however, was more efficacious than the effects of the other treatments (90% versus 40–50%). (2) Advanced lesion model. Twenty-four-week-old apoE −/− mice were treated with 0.03 or 0.1% CS-505 or 0.1% CI-1011 for 12 weeks. CS-505 at 0.1% revealed enhanced lesion reduction compared with 0.1% CI-1011 (77% versus 54%), whereas the plasma cholesterol-lowering effect of 0.1% CS-505 was almost the same as that of 0.1% CI-1011. Furthermore, immunohistochemical analysis demonstrated that CS-505 significantly reduced the number of macrophages and expression of matrix metalloproteinase (MMP)-2, MMP-9, and MMP-13. These data indicate that CS-505 can reduce and stabilize atherosclerotic lesions. This antiatherosclerotic activity is exerted via both cholesterol lowering and direct ACAT inhibition in plaque macrophages.

The Amount of Dietary Cholesterol Changes the Mode of Effects of (n-3) Polyunsaturated Fatty Acid on Lipoprotein Cholesterol in Hamsters

This study was designed to investigate the effects of the interaction between dietary (n-3) polyunsaturated fatty acids (PUFA) and different dietary cholesterol content on plasma and liver cholesterol in hamsters. Male Syrian hamsters consumed diets containing an incremental increase in dietary cholesterol content (0, 0.025, 0.05, 0.1 and 0.2%, w/w) with either (n-3) PUFA (21 g/100 g fatty acids) or (n-6) PUFA (37.4 g/100 g fatty acids) fat for 6 weeks. In hamsters fed the nonatherogenic diet (0 or 0.025% dietary cholesterol), very low density lipoprotein (VLDL)-cholesterol levels in the (n-3) PUFA group were not significantly different from those in the (n-6) PUFA group, and low density lipoprotein (LDL)-cholesterol levels in the (n-3) PUFA group were significantly lower than those in the (n-6) PUFA group. In contrast, in hamsters fed the atherogenic diet (0.1 or 0.2% dietary cholesterol), VLDL- and LDL-cholesterol levels in the (n-3) PUFA group were significantly higher than those in the (n-6) PUFA group, in a dose-dependent manner. When the hamsters were fed with 0, 0.025, 0.05, 0.1 or 0.2% (w/w) dietary cholesterol, high density lipoprotein (HDL) cholesterol concentration was significantly lower in the (n-3) PUFA group than those in the (n-6) PUFA group. Hepatic cholesteryl esters were significantly lower, while hepatic microsomal acyl-coenzyme A:cholesterol acyltransferase activity and VLDL-cholesteryl esters were significantly higher in hamsters fed (n-3) PUFA with the atherogenic diet (0.1 or 0.2% dietary cholesterol) than in those fed (n-6) PUFA with the atherogenic diet. Our results demonstrate that the amount of dietary cholesterol is an important factor in determining the mode and extent of effects of dietary (n-3) PUFA, especially on VLDL- and LDL-cholesterol levels. When dietary cholesterol intake was above 0.1% (w/w), the plasma cholesterol-lowering effect of (n-3) PUFA disappeared, and instead, it showed a cholesterol-increasing effect. However, the effects of dietary (n-3) PUFA on HDL-cholesterol are independent of dietary cholesterol content.

Isoflavones: their effects on cardiovascular risk and functions.

Isoflavones - plant polyphenols with oestrogenic activity - are becoming widely distributed in foods and sold as nutriceuticals. Their similarity to steroidal oestrogens has stimulated research into potential cardiovascular benefits. The two major areas, those of lipid lowering and of improved vascular function, are reviewed. A major plasma cholesterol lowering effect has not been sustained in recent publications. Relatively minor reductions in LDL-cholesterol or non-HDL-cholesterol have generally been reported, but studies in which no reduction was found have also been reported. Fewer publications have dealt with effects on vasculature, but these have been more consistent. Arterial compliance, a parameter of the elasticity or distensibility of large arteries, is improved by as much as has been reported for estrogens. Vasodilatory effects on the microcirculation with isoflavones or their metabolites may provide opportunities for pharmacological intervention. The metabolism of isoflavones is reviewed briefly in order to highlight its complexity. Although research has failed to demonstrate substantial cholesterol lowering with dietary isoflavones, consumption of legumes is generally to be encouraged as part of the overall strategy for lowering plasma lipids. The favourable effects of ingested or infused isoflavones on several parameters of arterial function suggest an alternative explanation for the apparent low prevalence of coronary disease in populations that eat legumes as a staple food. A better understanding of the pharmacokinetics and bioavailabilty of individual isoflavones is needed if definitive studies are to be designed.

2P-0562 Rosuvastatin reduces atherosclerosis development beyond and independently of its plasma cholesterol-lowering effect in APOE∗3-Leiden transgenic mice. Evidence for anti-inflammatory effects of rosuvastatin

2P-0562 Rosuvastatin reduces atherosclerosis development beyond and independently of its plasma cholesterol-lowering effect in APOE∗3-Leiden transgenic mice. Evidence for anti-inflammatory effects of rosuvastatin

2P-0570 The PPAR-α-agonist fenofibrate reduces development of atherosclerosis beyond and independently of its plasma cholesterol-lowering effect in APOE∗3-Leiden transgenic mice

2P-0570 The PPAR-α-agonist fenofibrate reduces development of atherosclerosis beyond and independently of its plasma cholesterol-lowering effect in APOE∗3-Leiden transgenic mice