Resveratrol Improves Endothelial Function

Abstract

Objective-Oxidative stress plays an important role in type 2 diabetes-related endothelial dysfunction. We hypothesized that resveratrol protects against oxidative stress-induced endothelial dysfunction in aortas of diabetic mice by inhibiting tumor necrosis factor ␣ (TNF␣)-induced activation of NAD(P)H oxidase and preserving phosphorylation of endothelial nitric oxide synthase (eNOS pidemiological studies indicate that the meditteranean diet that is rich in resveratrol, a plant polyphenol is associated with reduced risk of cardiovascular diseases, 1 which account for the majority of the mortality in type 2 diabetes. 2 Vascular dysfunction is the initial step in the occurrence of many disease states in the cardiovascular system concurrent with diabetes. 3 Obesity is an established risk factor for type 2 diabetes. Recent studies suggest that resveratrol, by activating silent mating type information regulation 2 homolog 1 (SIRT1), safely mimics the effects of dietary restriction in laboratory animals. 4 In diet-induced obese mice, resveratrol improves insulin sensitivity, lowers plasma glucose, and increases mitochondrial capacity. 5 Furthermore, resveratrol attenuates aortic dysfunction in aging and high fat-induced obesity animal models. 6 However, there is no study regarding the effects of resveratrol on insulin sensitivity and vascular dysfunction in type 2 diabetic mice.Oxidative stress is known to be the key mechanism in the pathogenesis of diabetes-related vascular dysfunction. Oxidative stress is attributable to excessive production of reactive oxygen species (ROS). The inactivation of nitric oxide (NO, a potent vasodilator synthesized by endothelial NO synthase [eNOS]) by ROS is recognized to be a crucial factor in reducing NO bioavailability and the development of endothelial dysfunction. 7 NAD(P)H oxidase is a key source of superoxide (O 2 ⅐Ϫ ) in the vasculature. 8 Previous work shows that anti-tumor necrosis factor-alpha (TNF␣) treatment inhibits NAD(P)H oxidase activation in coronary arterioles from type 2 diabetic mice. 9 TNF␣ is reported to downregulate eNOS expression in fat and muscle of obese rodents. 10 Several studies also reported that resveratrol

Exercise training improves endothelial function via adiponectin-dependent and independent pathways in type 2 diabetic mice

“…Proinflammatory cytokines impair endothelial function in animal models and in isolated human veins (3,10,33). Previous studies show that insulin resistance and T2D are associated with increased proinflammatory cytokines such as TNF-␣ and IL-6 as well as decreased plasma adiponectin (APN) (8,15,35,54). We hypothesize that exercise training (ET) improves endothelial function in the diabetic aorta by suppressing oxidative stress and inflammatory process thereby increasing NO bioavailability.…”

“…This improvement is due to the effects of ET in inhibiting inflammation and oxidative stress (APN-dependent) as well as in improving antioxidant enzyme (APN-independent) performance in T2D. cardiovascular disease; inflammation; superoxide; vascular biology TYPE 2 DIABETES (T2D) is associated with impairment in endothelial function characterized by impaired endothelial-dependent vasodilation, increased inflammatory cell, and platelet adhesion in both rodents and humans (22,32,41,42,54). Accumulating evidence suggests that endothelial dysfunction is an early stage of atherosclerosis (11,41).…”

“…Thus endothelial dysfunction with inflammatory cell and platelet adhesion may contribute to the development of atherosclerosis in T2D. Even though the mechanisms responsible for endothelial dysfunction are not fully elucidated, previous studies indicate that a decrease in nitric oxide (NO) bioavailability may play a central role in endothelial dysfunction in T2D (32,36,54).In addition, oxidative stress and chronic inflammation are important pathogenic factors in many diseases including T2D and cardiovascular diseases (CVD) such as stroke, coronary artery disease, and atherosclerosis (8,19,28,32). Previous studies indicated that reactive oxygen species (ROS) such as superoxide (O 2 ·Ϫ ) readily react with NO to form peroxynitrate (ONOO Ϫ ), which results in decreased NO bioavailability (8,10,32,47).…”

“…Thus endothelial dysfunction with inflammatory cell and platelet adhesion may contribute to the development of atherosclerosis in T2D. Even though the mechanisms responsible for endothelial dysfunction are not fully elucidated, previous studies indicate that a decrease in nitric oxide (NO) bioavailability may play a central role in endothelial dysfunction in T2D (32,36,54).…”

“…are not fully elucidated, previous studies indicate that a decrease in nitric oxide (NO) bioavailability may play a central role in endothelial dysfunction in T2D (32,36,54).…”