Resveratrol protects against atherosclerosis, but does not add to the antiatherogenic effect of atorvastatin, in APOE*3-Leiden.CETP mice (original) (raw)
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Atherosclerosis, 2009
Resveratrol, a polyphenolic constituent of red wine, is known for its anti-atherogenic properties and is thought to be beneficial in reducing the incidence of cardiovascular diseases (CVD). However, the mechanism of action by which it exerts its anti-atherogenic effect remains unclear. In this study, we investigated the relationship between the antioxidant effects of resveratrol and its ability to promote cholesterol efflux. We measured the formation of conjugated dienes and the rate of lipid peroxidation, and observed that resveratrol inhibited copper-and irradiation-induced LDL and HDL oxidation as observed by a reduction in oxidation rate and an increase in the lag phase (p < 0.05). We used DPPH screening to measure free radical scavenging activity and observed that resveratrol (0-50 M) significantly reduced the content of free radicals (p < 0.001). Respect to its effect on cholesterol homeostasis, resveratrol also enhanced apoA-1-mediated cholesterol efflux (r 2 = 0.907, p < 0.05, linear regression) by up-regulating ABCA-1 receptors, and reduced cholesterol influx or uptake in J774 macrophages (r 2 = 0.89, p < 0.05, linear regression). Incubation of macrophages (J774, THP-1 and MPM) with Fe/ascorbate ion, attenuated apoA-1 and HDL 3mediated cholesterol efflux whereas resveratrol (0-25 M) significantly redressed this attenuation in a dose-dependent manner (p < 0.001). Resveratrol thus appears to be a natural antioxidant that enhances cholesterol efflux. These properties make it a potential natural antioxidant that could be used to prevent and treat CVD.
Resveratrol in Cholesterol Metabolism and Atherosclerosis
Journal of Medicinal Food, 2012
Resveratrol, a natural polyphenol produced by plants in response to environmental stress, has received great attention during the past few years due to its beneficial roles in longevity and glucose homeostasis. Resveratrol has been found to display antioxidant, anti-inflammatory, antifibrotic, and cardioprotective properties. Resveratrol reduces platelet aggregation, induces vasorelaxation, limits endothelial activation, and modulates lipid and lipoprotein metabolism. Although the mechanisms of action of resveratrol have not been completely defined, there is evidence that some of the effects of resveratrol may be mediated via activation of sirtuin 1 and AMP-activated protein kinase and through inhibition of the pleiotropic transcription factor nuclear factor jB. Pathways proposed to underlie resveratrol-mediated cardioprotection include reduction of oxidative stress and activation of endothelial nitric oxide synthase. Adenosinergic mechanisms may play a role in its atheroprotective activity. The ability of the nutraceutical resveratrol to positively influence the future treatment of cardiovascular disease is discussed.
Archives of Biological Sciences, 2019
Resveratrol is a polyphenolic compound that exhibits antiinflammatory and cardioprotective properties. In this study we investigated the protective role of resveratrol on the inflammatory activation of macrophages during pathogenesis of atherosclerosis. Macrophage Ana-1 cells were stimulated by cholesterol and resveratrol, and the cell culture supernatant was collected to treat human umbilical vein endothelial cells (HUVECs). The release of IL-1? into the Ana-1 cell supernatant was quantified by ELISA. Expression of the adhesion molecule ICAM-1 and E-selectin in HUVECs were examined by Western-blotting. Additionally, the adhesion of monocytes in HUVECs under different conditions was tested by cell adhesion analyses. The results indicated that the high cholesterol treatment increased the expression level of IL-1?, while pretreatment with resveratrol inhibited this induction of IL-1? in Ana-1 cells. Resveratrol inhibited the adhesion of monocytes to the endothelium at least partly thr...
Oxidative medicine and cellular longevity, 2014
the proinflammatory M1 subset and the anti-inflammatory M2 one. 7-oxo-cholesterol, the most abundant cholesterol autoxidation product within atherosclerotic plaque, is able to skew the M1/M2 balance towards a proinflammatory profile. In the present study, we explored the ability of the polyphenolic compound resveratrol to counteract the 7-oxo-cholesterol-triggered proinflammatory signaling in macrophages. Resveratrol-pretreated human monocyte-derived M1 and M2 macrophages were challenged with 7-oxo-cholesterol and analyzed for phenotype and endocytic ability by flow cytometry, for metalloproteinase- (MMP-) 2 and MMP-9 by gelatin zymography, and for cytokine, chemokine, and growth factor secretome by a multiplex immunoassay. We also investigated the NF-κB signaling pathway. In the M1 subset, resveratrol prevented the downregulation of CD16 and the upregulation of MMP-2 in response to 7-oxo-cholesterol, whereas in M2 macrophages it prevented the upregulation of CD14, MMP-2, and MMP-9 ...
International Journal of Cardiology, 2013
Resveratrol has been proclaimed as an anti-aging compound to prevent and treat chronic conditions, including cardiovascular disease, diabetes mellitus and neurodegenerative disorders[1]. Though resveratrol's potential utility in preventive medicine has been demonstrated using animal models [2], few clinical trials have evaluated the effects of resveratrol on gene expression or clinically relevant biomarkers in healthy individuals. Trials evaluating cardiovascular risk generally measure plasma inflammatory biomarkers, including interleukins (IL) 1β, IL-6, Interferon Gamma (IFN-γ), Tumor Necrosis Factor alpha (TNF-α), but do not consider how components in plasma may interactively drive convergent endothelial cellular responses that contribute to the pathogenesis of atherosclerosis, including release of chemokines, such as IL-8 and activation of Vascular Cell Adhesion Molecule (VCAM) and Intercellular Adhesion Molecule (ICAM) [3-5]. This clinical trial evaluated the effects of one month resveratrol treatment on endothelial response
Resveratrol and Cardiovascular Diseases
Nutrients, 2016
The increased incidence of cardiovascular diseases (CVDs) has stimulated research for substances that could improve cardiovascular health. Among them, resveratrol (RES), a polyphenolic compound notably present in grapes and red wine, has been involved in the "French paradox". RES is known for its antioxidant and anti-inflammatory properties and for its ability to upregulate endothelial NO synthase (eNOS). RES was able to scavenge ‚ OH/O 2 ‚´a nd peroxyl radicals, which can limit the lipid peroxidation processes. Moreover, in bovine aortic endothelial cells (BAEC) under glucose-induced oxidative stress, RES restored the activity of dimethylargininedimethylaminohydrolase (DDAH), an enzyme that degrades an endogenous inhibitor of eNOS named asymmetric dimethylarginine (ADMA). Thus, RES could improve ‚ NO availability and decrease the endothelial dysfunction observed in diabetes. Preclinical studies have made it possible to identify molecular targets (SIRT-1, AMPK, Nrf2, NFκB. . .); however, there are limited human clinical trials, and difficulties in the interpretation of results arise from the use of high-dose RES supplements in research studies, whereas low RES concentrations are present in red wine. The discussions on potential beneficial effects of RES in CVDs (atherosclerosis, hypertension, stroke, myocardial infarction, heart failure) should compare the results of preclinical studies with those of clinical trials.
Cardiovascular Protective Effects of Resveratrol
Cardiovascular Drug Reviews, 2006
Resveratrol (3,4¢,5-trihydroxy-trans-stilbene), a phytoalexin found in grape skins, peanuts, and red wine, has been reported to have a wide range of biological and pharmacological properties. It has been speculated that at low doses (such as consumed in the common diet) resveratrol may have cardioprotective activity. In this article we describe recent in vitro and in vivo studies in animal models. The results of these studies suggest that resveratrol modulates vascular cell function, inhibits LDL oxidation, suppresses platelet aggregation and reduces myocardial damage during ischemia-reperfusion. Although the reported biological data indicate that resveratrol is a highly promising cardiovascular protective agent, more studies are needed to establish its bioavailability and in vivo cardioprotective effects, particularly in humans.
Resveratrol: Effects on Lipids and Cardiovascular Risk
Current Cardiovascular Risk Reports, 2013
For several decades, there has been increasing interest in the possible use of resveratrol as a preventative agent in cardiovascular disease. Resveratrol exerts numerous effects on adipocyte, hepatocyte, and endothelial cell development and function. Many investigations have demonstrated the ability of resveratrol to regulate the adipocyte lifecycle, lipid synthesis, and improve hepatic lipid metabolism. Resveratrol has numerous vascular protective effects on endothelial tissue, including its antiplatelet activity. Resveratrol also reduces intracellular oxidative stress. Animal models of obesity and cardiovascular diseases have yielded important contributions to our understanding of the effects of resveratrol on the vasculature and the risk for pathology. In limited human studies, resveratrol reduces the release of proinflammatory cytokines and improves systemic glucose and insulin regulation and decreases cellular oxidative stress. Therefore, resveratrol has significant potential as both a prophylactic and treatment agent. However additional studies are required to more completely characterize its impacts on human physiology and its benefits in the setting of disease.