The beneficial effects of virgin olive oil against oxidative stress induced by hypercholesterolemia in rats

Cardiovascular disease(CVD) remains the major cause of mortality in the world, typically claiming a third of all deaths. The primary cause of CVD is atherosclerosis. Therefore, timely prevention and therapy of atherosclerosis are able to reduce the risk of the development of its clinical manifestations. Anti-atherosclerotic activity of medicinal plants mainly appears in their multiple effects.This study was carried out to evaluate the hypolipidemic activity of virgin olive oil in experimentally induced hyperlipemic Wistar. A total of 24 rats were randomly allocated to 4 equal groups and treated as follows for 50 days: (1) Normal control (NC); that were fed with a standart diet; (2) High Cholesterol Diet Control (HCD); which received high cholesterol diet for 50 days; (3) Animals receiving high cholesterol diet for 50 days, after this period the animals are fed for eight days by the standard foodand receiving by gavage virgin olive oil (HCD+VOO) and(4) Animals fed for eight days with the standard food and receiving by gavage olive oil (VOO). High Cholesterol Diet containing yolk egg and coconut oil. Results showed that olive oil caused a significant (p < 0.01) reduction in serum levels of Total Cholesterol (TC), Triglycerides (TG), Low­Density Lipoprotein Cholesterol (LDL) and Atherogenic Index Serum (AIS). The results also demonstrated a significant (p < 0.01) increase in High­Density Lipoprotein Cholesterol (HDL). Moreover, virgin olive oil induced a significant reduction in liver lipid content. On the other hand, a High cholesterol diet induced oxidative stress was measured by estimating reduced glutathione level and amount of thiobarbituric acid reactive substances (TBARS) formed as an index of lipid peroxidation in a liver and a heart. Virgin olive oil supplementation attenuated all these variations. Our observations of the study indicate that the virgin olive oil has a significant antihyperlipidemic potential.

Beneficial Effects of Ursolic Acid and Its Derivatives-Focus on Potential Biochemical Mechanisms in Cardiovascular Conditions.

Ursolic acid (UA) is a natural pentacyclic triterpenoid found in a number of plants such as apples, thyme, oregano, hawthorn and others. Several in vitro and in vivo studies have presented its anti-inflammatory and anti-apoptotic properties. The inhibition of NF-κB-mediated inflammatory pathways and the increased scavenging of reactive oxygen species (ROS) in numerous ways seem to be the most beneficial effects of UA. In mice and rats, administration of UA appears to slow down the development of cardiovascular diseases (CVDs), especially atherosclerosis and cardiac fibrosis. Upregulation of endothelial-type nitric oxide synthase (eNOS) and cystathionine-λ-lyase (CSE) by UA may suggest its vasorelaxant property. Inhibition of metalloproteinases activity by UA may contribute to better outcomes in aneurysms management. UA influence on lipid and glucose metabolism remains inconsistent, and additional studies are essential to verify its efficacy. Furthermore, UA derivatives appear to have a beneficial impact on the cardiovascular system. This review aims to summarize recent findings on beneficial effects of UA that may make it a promising candidate for clinical trials for the management of CVDs.

Sesamol supplementation alleviates nonalcoholic steatohepatitis and atherosclerosis in high-fat, high carbohydrate and high-cholesterol diet-fed rats.

Sesamol, a major ingredient in sesame seeds (Sesamum indicum L.) and its oil, is considered a powerful functional food ingredient. However, few studies have investigated its effects on high-fat, high carbohydrate and high-cholesterol (HF-HCC) diet-induced nonalcoholic steatohepatitis (NASH) complicated with atherosclerosis. The present study elucidates the protective effects of sesamol against NASH and atherosclerosis in HF-HCC diet-fed rats. Sprague-Dawley rats were supplemented with or without sesamol in drinking water (0.05 mg mL-1, 0.1 mg mL-1 and 0.2 mg mL-1) from the beginning to end. At the end of the experiment, sesamol supplementation suppressed HF-HCC diet-induced body weight gain and increased absolute liver and adipose tissue weights in rats. Serum biochemical analyses showed that sesamol supplementation improved HF-HCC diet-induced metabolism disorders and damaged vascular endothelial function. Histological examinations displayed that dietary sesamol not only alleviated hepatic balloon degeneration, steatosis, inflammation and fibrosis, but also mitigated lipid accumulation and fibrous elements in the aorta arch in HF-HCC diet-fed rats. In addition, sesamol supplementation inhibited hepatic NOD-like receptor protein 3 (NLRP3) expression and ERS-IRE1 signaling pathway activation. Moreover, sesamol treatment decreased uric acid levels both in serum and the liver by its effect on the inhibition of xanthine oxidase (XO) activity and/or its expression, which might be closely associated with the inhibitions of NLRP3 expression and ERS-IRE1 signaling pathway activation in HF-HCC diet-fed rats. These findings demonstrated that sesamol alleviated NASH and atherosclerosis in HF-HCC diet-fed rats, and may be a potent dietary supplement for protection against these diseases.

Malondialdehyde (MDA) Production in Atherosclerosis Supplemented with Steamed Tomato.

Background and Objective: Malondialdehyde (MDA) may increase influenced by free radicals due to lipid oxidation. Tomato induction considers able to prevent free radical damage and atherosclerosis. Therefore, this study aims to understand the effect of steamed-tomato extracts on MDA and its potential as an early diagnosis of atherosclerosis. Materials and Methods: A total of 24 healthy 12 weeks-old male-rats were divided into four treatment groups, equally. A normal control group (K1) was rats with placebo treatment. A negative control group (K2) was the rats supplemented with 2 mL kg-1 b.wt. per day of cholesterol until cholesterol. A K3 group was atherosclerosis rats given with 20 mg kg-1 b.wt. per day of atorvastatin and a K4 was atherosclerotic rats supplemented with 16 mg kg-1 b.wt. per day of tomato extract. All treatments were carried out for 60 consecutive days. Results: Tomato extract in the K4 group was succeeded in lowering MDA production. Carotenoid compounds in tomato extract are well known to be prevention agents against lipid oxidation and inhibit free radicals. MDA levels have increased significantly in atherosclerosis conditions, making it potentially noticeable during early atherosclerotic, therefore, potentially developed as biomarkers. Conclusion: MDA levels increase significantly and simultaneously after high cholesterol diets and in line with lipid parameters and damaged blood vessels. The steamed-tomato extract can reduce MDA, lipids levels and protect endothelial from lipid oxidation. More research should be conducted to breakdown the MDA function in the molecular pathway, including MDA correlation to microRNA expression and cell signaling.

Dietary iron overload mitigates atherosclerosis in high-fat diet-fed apolipoprotein E knockout mice: Role of dysregulated hepatic fatty acid metabolism.

The atherosclerosis "iron hypothesis" generates a fair amount of debate since it has been proposed. Here, we revisited the "iron hypothesis" by examining whether dietary iron overload would intensify iron deposition in plaques and thus lead to further exacerbation of atherosclerosis in apolipoprotein E knockout (ApoE KO) mice. ApoE KO mice were fed either a normal chow diet (ND) or a high fat diet (HFD) supplemented with or without 2% carbonyl iron (Fe) for 16 weeks. However, contrary to our assumption, dietary iron overloading did not intensify, but rather diminished the atherosclerotic lesion area by 65.3%, which was accompanied by significantly decreased serum total cholesterol, triglyceride and low-density lipoprotein cholesterol contents, together with hepatic lipid accumulation decline, despite the evident existence of aortic iron accumulation and the typical signs of iron overload in ApoE KO mice. Using isobaric tag for absolute quantification (iTRAQ) proteomics approach, hepatic CD36 and fatty acid binding proteins-mediated fatty acid (FA) uptake and trafficking impairment were identified as the key potential pathomechanisms by which iron overload diminishes atherosclerotic lesions. Furthermore, downstream hepatic FA de novo biosynthesis was enhanced and FA oxidation was inhibited to compensate for the FA deficiency triggered by iron overload-impaired fatty acid uptake and trafficking. Our findings suggested that dietary iron overload is not atherogenic in ApoE KO mice, and more research efforts are warranted to revisit the "iron hypothesis" of atherosclerosis.

Dietary Fruit and Vegetable Supplementation Suppresses Diet-Induced Atherosclerosis in LDL Receptor Knockout Mice.

BACKGROUND: Epidemiologic studies suggest that fruit and vegetable (F&V) consumption is inversely associated with incidence of cardiovascular disease (CVD). However, evidence for causality is lacking, and the underlying mechanisms are not well understood. OBJECTIVES: We aimed to determine whether there is a causal relation between consuming high levels of F&V and prevention of atherosclerosis, the hallmark of CVD pathogenesis. Furthermore, the underlying mechanisms were determined. METHODS: Six-week-old male LDL receptor-knockout mice were randomly assigned to 3 diet groups (12 mice/group) for 20 wk: control (CON, 10% kcal fat, 0.20 g/kg cholesterol), atherogenic (Ath, 27% kcal fat, 0.55 g/kg cholesterol), and Ath supplemented with 15% F&V (Ath + FV) (equivalent to 8-9 servings/d in humans). F&V was added as a freeze-dried powder that was prepared from the 24 most commonly consumed F&Vs in the United States. Body weight, aortic atherosclerotic lesion area, hepatic steatosis area, serum lipid profile and proinflammatory cytokine TNF-α concentrations, gut microbiota, and liver TNF-α and fatty acid synthase (Fasn) mRNA concentrations were assessed. RESULTS: F&V supplementation did not affect weight gain. Mice fed the Ath + FV diet had a smaller aortic atherosclerotic lesion area (71.7% less) and hepatic steatosis area (80.7% less) than those fed the Ath diet (both P < 0.001) independent of impact on weight, whereas no difference was found between Ath + FV and CON groups in these 2 pathologic markers. Furthermore, F&V supplementation prevented Ath diet-induced dyslipidemia (high concentrations of serum TG and VLDL cholesterol and lower concentrations of HDL cholesterol), reduced serum TNF-α concentration (by 21.5%), suppressed mRNA expression of liver TNF-α and Fasn, and ameliorated Ath-induced gut microbiota dysbiosis. CONCLUSIONS: Our results indicate that consuming a large quantity and variety of F&Vs causally attenuates diet-induced atherosclerosis and hepatic steatosis in mice. These effects of F&Vs are associated with, and may be mediated through, improved atherogenic dyslipidemia, alleviated gut dysbiosis, and suppressed inflammation.

Medium-, long- and medium-chain-type structured lipids ameliorate high-fat diet-induced atherosclerosis by regulating inflammation, adipogenesis, and gut microbiota in ApoE-/- mice.

Accumulating evidence has suggested that medium-, long-, and medium-chain (MLM) structured lipids have anti-obesity effects, but whether they can alleviate the development of atherosclerosis (AS) and affect the composition of the gut microbiota in high-fat diet-fed ApoE-/- mice has not been elucidated. The present study found that MLM structured lipid supplementation could significantly decrease obesity-related parameters compared with high-fat diet alone in ApoE-/- mice. Additionally, MLM structured lipids could significantly decrease the blood glucose and increase the serum total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) levels. Additionally, high-dose MLM structured lipids supplementation could reduce the area of atherosclerotic lesions and decrease the expression of VCAM-1, MCP-1 and CD68, which are related to inflammation in aortic tissue. Further analysis showed that MLM structured lipids could significantly reduce lipid accumulation in the adipose tissue of high-fat diet-fed ApoE-/- mice. The relative protein expression of SREBP-1, ACC, FAS, C/EBPα and PPARγ was decreased and the ratio of p-AMPK/AMPK was increased in epididymis white adipose tissue (eWAT) after MLM structured lipids treatment. Additionally, MLM structured lipids supplementation regulated the bacterial composition, including reducing the Firmicutes/Bacteroidetes ratio, increasing the relative abundance of short-chain fatty acid-producing bacteria (Blautia and Anaerotruncus), decreasing the relative abundance of [Ruminococcus] torques group, Ruminiclostridium 9, Catenibacterium and [Eubacterium] fissicatena group. Spearman's correlation analysis revealed significant correlations between changes in the gut microbiota and atherosclerosis-related indices. The results demonstrated that the alleviating effects of MLM structured lipids supplementation on AS in high-fat diet-fed ApoE-/- mice were closely related to reshaping the composition of the gut microbiota.

Daily watermelon consumption decreases plasma sVCAM-1 levels in overweight and obese postmenopausal women.

Postmenopausal status is associated with an increase in total and abdominal body fat as well as increased incidence of insulin resistance and cardiovascular disease. The purpose of this study was to determine if watermelon supplementation affects select systemic markers of atherosclerosis and measures of insulin resistance in overweight and obese postmenopausal women. We hypothesized that overweight and obese postmenopausal women consuming 100% watermelon puree daily for 6 weeks would have improved levels of select systemic markers connected with cardiovascular disease without changing markers of insulin resistance. To test this hypothesis, overweight and obese postmenopausal women were recruited to participate in this study. Participants were randomly assigned to either the control group (no intervention) or the watermelon puree group (WM) for 6 weeks. Plasma concentration of markers connected with atherosclerosis and glycemic control were measured pre- and poststudy. A significant 6% decrease in soluble vascular cell adhesion molecule-1 occurred pre- to poststudy in WM, P = .003. The pattern of change in fasting blood glucose (P = .633), insulin (P = .158), and homeostatic model assessment-estimated insulin resistance (P = .174) did not differ between groups. Pre- to poststudy increases were measured in the fasting plasma concentration of l-arginine (8%, P = .005), cis-lycopene (32%, P = .003), and trans-lycopene (42%, P = .003) in WM. We conclude that 6 weeks of watermelon supplementation improved soluble vascular cell adhesion molecule-1 levels, a marker connected to atherogenesis, independent of changes in body composition or glycemic control.

The Mediterranean diet decreases prothrombotic microvesicle release in asymptomatic individuals at high cardiovascular risk.

BACKGROUND & AIMS: Circulating microvesicles (cMV) are small phospholipid-rich vesicles that contribute to the atherothrombotic process, and are biomarkers of cardiovascular disease (CVD) burden and progression. Diet is a cornerstone for CVD prevention, but dietary effects on cMV shedding are poorly characterized. We aimed at assessing the long term effects of a Mediterranean diet compared to a low-fat diet (LFD) on MV shedding by cells of the blood and vascular compartments in patients at high cardiovascular risk treated as per guidelines. METHODS: A total of 155 participants from the PREDIMED trial free of cardiovascular events after a mean follow-up of 5 years (n = 53 from the Mediterranean diet supplemented with extra-virgin olive oil -EVOO-; n = 49 from the Mediterranean diet supplemented with mixed nuts -Nuts-; and n = 53 from the LFD) were included in the study. At baseline and after one-year intervention, cMV were quantified and characterized by flow cytometry to identify their activated parental cell origin and prothrombotic potential by Annexin V (AV) binding. RESULTS: After one year of dietary intervention, platelet-derived PAC-1+/AV+ and CD62P+/AV+ cMV concentrations were lower in the Nuts group compared with the LFD and EVOO interventions (P = 0.036 and 0.003, respectively). In addition, prothrombotic cMV carrying tissue factor (CD142+/AV+) and CD11a+/AV+ cMV derived from activated cells, were significantly lower in both Mediterranean diet (EVOO and Nuts) interventions compared to one year of LFD (P < 0.0001 and 0.028, respectively). SMAα+/AV- cMV were lower in the LFD compared to the Nuts group after one year of intervention (P = 0.038). CONCLUSIONS: cMV are markers of cell activation and vascular injury that appear to be sensitive to dietary changes. Following a Mediterranean diet rich in EVOO or nuts is associated with lower cell activation towards a pro-atherothrombotic phenotype, suggesting a delay in the development of CV complications.

The Potential of Probiotics in the Prevention and Treatment of Atherosclerosis.

Atherosclerosis, the underlying cause of cardiovascular diseases such as myocardial infarction, cerebrovascular accident, and peripheral vascular disease, is the leading cause of global mortality. Current therapies against atherosclerosis, which mostly target the dyslipidemia associated with the disease, have considerable residual risk for cardiovascular disease together with various side effects. In addition, the outcomes from clinical trials on many promising pharmaceutical agents against atherosclerosis (e.g., low-dose methotrexate, inhibitors against cholesteryl ester transfer protein) have been disappointing. Nutraceuticals such as probiotic bacteria have, therefore, generated substantial recent interest for the prevention of atherosclerosis and potentially as add-ons with current pharmaceutical drugs. This review will discuss the current understanding of the anti-atherogenic actions of probiotics from preclinical and clinical studies together with their potential underlying mechanisms of action.

Replacing Saturated Fat With Unsaturated Fat in Western Diet Reduces Foamy Monocytes and Atherosclerosis in Male Ldlr-/- Mice.

OBJECTIVE: A Mediterranean diet supplemented with olive oil and nuts prevents cardiovascular disease in clinical studies, but the underlying mechanisms are incompletely understood. We investigated whether the preventive effect of the diet could be due to inhibition of atherosclerosis and foamy monocyte formation in Ldlr-/- mice fed with a diet in which milkfat in a Western diet (WD) was replaced with extra-virgin olive oil and nuts (EVOND). Approach and Results: Ldlr-/- mice were fed EVOND or a Western diet for 3 (or 6) months. Compared with the Western diet, EVOND decreased triglyceride and cholesterol levels but increased unsaturated fatty acid concentrations in plasma. EVOND also lowered intracellular lipid accumulation in circulating monocytes, indicating less formation of foamy monocytes, compared with the Western diet. In addition, compared with the Western diet, EVOND reduced monocyte expression of inflammatory cytokines, CD36, and CD11c, with decreased monocyte uptake of oxLDL (oxidized LDL [low-density lipoprotein]) ex vivo and reduced CD11c+ foamy monocyte firm arrest on vascular cell adhesion molecule-1 and E-selectin-coated slides in an ex vivo shear flow assay. Along with these changes, EVOND compared with the Western diet reduced the number of CD11c+ macrophages in atherosclerotic lesions and lowered atherosclerotic lesion area of the whole aorta and aortic sinus. CONCLUSIONS: A diet enriched in extra-virgin olive oil and nuts, compared with a Western diet high in saturated fat, lowered plasma cholesterol and triglyceride levels, inhibited foamy monocyte formation, inflammation, and adhesion, and reduced atherosclerosis in Ldlr-/- mice.

Fish Oil Is More Potent than Flaxseed Oil in Modulating Gut Microbiota and Reducing Trimethylamine-N-oxide-Exacerbated Atherogenesis.

Trimethylamine-N-oxide (TMAO) is a risk factor for atherosclerosis. We compared the potency of fish oil with flaxseed oil in reducing TMAO-exacerbated atherogenesis. Five groups of ApoE-/- mice were given one of five diets, namely, a low-fat diet, a Western high fat diet (WD), a WD plus 0.2% TMAO, and two WDs containing 0.2% TMAO with 50% lard being replaced by flaxseed oil or fish oil. TMAO accelerated atherosclerosis and disturbed cholesterol homeostasis. Compared with flaxseed oil, fish oil was more effective in inhibiting TMAO-induced atherogenesis by lowering plasma cholesterol and inflammatory cytokines. Both oils could reverse TMAO-induced decrease in fecal acidic sterols. Fish oil promoted fecal output of neutral sterols and downregulated hepatic cholesterol biosynthesis. Fish oil was more effective than flaxseed oil in promoting the growth of short-chain fatty acid-producing bacteria and lowering microbial generation of lipopolysaccharide. In conclusion, fish oil is more potent than flaxseed oil to ameliorate TMAO-exacerbated atherogenesis.

Calcium-rich diet and vitamin D supplementation improves lipid profiles and reduces atherogenic index in high salt fed male Wistar rat.

To ascertain the effect of calcium rich diet and/ or vitamin D supplementation on atherogenic parameters in high salt loaded rats. Thirty male rats were randomly assigned into five groups of six rats each, namely; control; salt only; salt + Calcium; salt + Vit. D and salt + Vit. D + Calcium. High salt diet constituted 8% NaCl diet + 1% NaCl drinking water, while calcium diet was made from 2.5% CaCl2 diet. Serum lipids and atherogenic indices were estimated using standard laboratory procedures. The control rats took normal rodent chow, the feeding lasted 6 weeks. Rats fed high salt diet only had significantly (p<0.05) reduced high density lipoprotein cholesterol levels, however this was significantly (p<0.05) increased upon treatment with calcium rich diet and vitamin D supplementation. The high salt groups placed on Vit. D and/or calcium diet supplementation had a significant (p<0.05) decrease in low density lipoproteins, total cholesterol and atherogenic indices (cardiac risk ratio, atherogenic coefficient and atherogenic index of plasma) compared to the group fed on high salt only. These results suggest the ameliorative potentials of calcium rich diets and vitamin D supplementation against atherogenic tendencies and possibly cardiovascular diseases.

Dietary polyphenols for atherosclerosis: A comprehensive review and future perspectives.

Atherosclerosis is one of the most prevalent reasons for premature death in adults. Despite the several conventional drugs in the market; many patients are not completely treated. Here we comprehensively review current clinical evidence regarding the efficacy of dietary polyphenols in atherosclerosis and related complications. PubMed, Cochrane library and Scopus were searched from inception until August 2016 to obtain clinical trials in which polyphenols were evaluated in cardiovascular parameters related to atherosclerosis. From total of 13031 results, 49 clinical trials were finally included. Tyrosol derivatives from virgin olive oil, catechins and theaflavins from green and black tea, cocoa polyphenols, and red grape resveratrol, as well as anthocyanins were the most studied polyphenolic compounds which could regulate lipid profile, inflammation and oxidative stress, blood pressure, endothelial function, and cell adhesion molecules. The most important limitations of the included trials were small sample size, short follow up, and unqualified methodology. Future well-designed clinical trials are necessary to provide better level of evidence for clinical decision making.

Dietary antioxidant intake decreases carotid intima media thickness in women but not in men: A cross-sectional assessment in the Kardiovize study.

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

Comparison between red wine and isolated trans-resveratrol on the prevention and regression of atherosclerosis in LDLr (-/-) mice.

Moderate consumption of red wine has been widely associated with reduced cardiovascular risk, mainly due to its composition in phenolic compounds with antioxidant activity, such as resveratrol. The objective of this study was to compare the effect of red wine vs. trans-resveratrol consumption on the prevention and regression of atherosclerosis in LDLr (-/-) mice. This study consisted of two protocols: "Prevention" (PREV) and "Regression" (REGR). Both protocols included four groups: red wine (WINE), dealcoholized red wine (EXT), trans-resveratrol (RESV), and control (CONT). In PREV protocol, animals received a regular diet for 8 weeks and then switched to an atherogenic diet for the following 8 weeks, while the opposite was performed in REGR. Animals that received atherogenic diet after an initial period of standard diet (PREV) gained more body weight (39.25±2.30%) than the opposite (29.27±1.91%, P=.0013), suggesting an interaction between age and weight gain. Trans-resveratrol showed the highest hypocholesterolemic effect during PREV, reducing total cholesterol, LDL-C, VLDL-C and HDL-C. Supplementation with trans-resveratrol and dealcoholized red wine changed the fatty acids profile in the liver in both protocols, leading to an increase of MDA concentrations and SOD activity in the PREV protocol. In conclusion, supplementation with trans-resveratrol, red wine and the same wine without alcohol altered biomarkers of oxidative stress and lipidemia but had no effect on the prevention or regression of fatty streaks. These data suggest that cardiovascular protection associated with the "French Paradox" may be a result of synergistic effects between wine and the Mediterranean diet.

Prevention of Atherosclerosis by Berries: The Case of Blueberries.

Berry consumption has been associated with cardiovascular disease prevention in recent years. Atherosclerosis is one of the major causes of cardiovascular diseases. However, research on the prevention of atherosclerosis through consuming individual whole berries, specifically direct evidence, remains scarce. Therefore, further elucidating the role that berries play in the prevention of atherosclerosis is warranted. In this perspective, blueberries were selected to articulate research strategies for studying atheroprotective effects of berries. Studies from human subjects and various animal models are summarized. The mechanisms by which blueberries may act, through reducing oxidative stress, decreasing inflammation, improving endothelial dysfunction, regulating cholesterol accumulation and trafficking, along with potentially influencing gut microbiota, are also discussed. Blueberries contain high levels of polyphenolic compounds, which were widely indicated as major bioactive compounds. Nonetheless, the metabolites/catabolites after blueberry consumption, such as simple phenolic acids, rather than original compounds in berries, may be the actual in vivo bioactive compounds. Future research should focus on obtaining more direct evidence, preferably in humans, understanding of the mechanisms of action at the molecular level, and identifying bioactive compounds as well as which compounds act synergistically to convey health benefits. The research strategy discussed here may also be applied to the studies of other fruits and berries.

Sesame Oil and an Aqueous Extract Derived from Sesame Oil Enhance Regression of Preexisting Atherosclerotic Lesions in Low-Density Lipoprotein Receptor Knockout Mice.

Diet and exercise are recommended both as a prophylactic and as a therapeutic approach for patients with established coronary artery disease. We previously reported that sesame oil (SESO) and its aqueous extract (SOAE) showed antiatherosclerotic and anti-inflammatory properties. We also observed that genes involved in reverse cholesterol transport (RCT) might be activated. In this study, we tested whether post-treatment with SESO or SOAE would reduce preexisting atherosclerosis by enhancing RCT. Female low-density lipoprotein receptor knockout (LDL-R-/-) mice were fed an atherogenic diet for 3 months, followed by post-treatment with either control or SESO or SOAE for 1 month. Plasma lipids and atherosclerotic lesions were quantified at the end of the study. RNA was extracted from the aortic tissues and used for real-time polymerase chain reaction analysis. SESO and SOAE post-treatment significantly reduced atherosclerotic lesions in LDL-R-/- mice compared to controls. No significant change in plasma cholesterol, triglyceride, or LDL cholesterol levels was observed. Aortic gene analysis showed that the SESO/SOAE post-treatment reduced inflammatory gene expression and induced genes involved in cholesterol metabolism and RCT. This is the first study that demonstrates that post-treatment with SESO and SOAE could be an effective treatment for preexisting atherosclerosis and inflammation. The study also may suggest that reducing inflammation might be conducive to an accelerated regression of lesions.

Dietary Mannan Oligosaccharides Modulate Gut Microbiota, Increase Fecal Bile Acid Excretion, and Decrease Plasma Cholesterol and Atherosclerosis Development.

SCOPE: Mannan oligosaccharides (MOS) have proven effective at improving growth performance, while also reducing hyperlipidemia and inflammation. As atherosclerosis is accelerated both by hyperlipidemia and inflammation, we aim to determine the effect of dietary MOS on atherosclerosis development in hyperlipidemic ApoE*3-Leiden.CETP (E3L.CETP) mice, a well-established model for human-like lipoprotein metabolism. METHODS AND RESULTS: Female E3L.CETP mice were fed a high-cholesterol diet, with or without 1% MOS for 14 weeks. MOS substantially decreased atherosclerotic lesions up to 54%, as assessed in the valve area of the aortic root. In blood, IL-1RA, monocyte subtypes, lipids, and bile acids (BAs) were not affected by MOS. Gut microbiota composition was determined using 16S rRNA gene sequencing and MOS increased the abundance of cecal Bacteroides ovatus. MOS did not affect fecal excretion of cholesterol, but increased fecal BAs as well as butyrate in cecum as determined by gas chromatography mass spectrometry. CONCLUSION: MOS decreased the onset of atherosclerosis development via lowering of plasma cholesterol levels. These effects were accompanied by increased cecal butyrate and fecal excretion of BAs, presumably mediated via interactions of MOS with the gut microbiota.

Cereal Fiber Ameliorates High-Fat/Cholesterol-Diet-Induced Atherosclerosis by Modulating the NLRP3 Inflammasome Pathway in ApoE-/- Mice.

Cereal fiber is associated with decreasing the risk of cardiovascular diseases. However, whether cereal fiber modulates inflammatory response and improves atherosclerosis remains unclear. This study evaluated the anti-atherosclerotic effect of cereal fibers from oat or wheat bran and explored the potential anti-inflammatory mechanisms. Male ApoE-/- mice were given a high-fat/cholesterol (HFC) diet or a HFC diet supplemented with 0.8% oat fiber or wheat bran fiber. After 18 weeks of the feeding period, serum lipids and inflammatory cytokines were measured. The relative protein levels of the nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway and nuclear factor κB (NF-κB) were determined by the western blot method in aorta tissues. Pathologically, oat fiber and wheat fiber significantly reduced atherosclerotic plaques by 43.3 and 27.1%, respectively. Biochemically, cereal fiber markedly decreased the protein levels of myeloid differentiation factor 88 (MyD88) and toll-like receptor 4 (TLR4) in aortic tissues. The expression of NF-κB was similarly inhibited by both cereal fibers. In comparison to wheat bran fiber, oat fiber had greater effects in reducing the plague size and inhibiting TLR4/MyD88/NF-κB pathways. Such differences might come from modulation of the NLRP3 inflammasome pathway because the expressions of the cleavage of caspase-1 and interleukin (IL)-1ß were inhibited only by oat fiber. The present study demonstrates that cereal fibers can attenuate inflammatory response and atherosclerosis in ApoE-/- mice. Such effects are pronounced with oat fiber and likely mediated by specific inhibition of oat fiber on the NLRP3 inflammasome pathway.