Vascular Dysfunction in Aging: Potential Effects of Resveratrol, an Anti- Inflammatory Phytoestrogen

Abstract

Epidemiological studies demonstrated that even in the absence of other risk factors (e.g. diabetes, hypertension, hyperhomocysteinemia, hypercholesterolemia), advanced age itself significantly increases cardiovascular morbidity by enhancing vascular oxidative stress and inflammation. Because the population in the Western world is rapidly aging, there is a substantial need for pharmacological interventions that delay the functional decline of the cardiovascular system. Resveratrol is an atoxic phytoestrogen found in more than 70 plants including grapevine and berries. Recent data suggest that nutritional intake of resveratrol and other polyphenol compounds may contribute to the "French paradox", the unexpectedly low cardiovascular morbidity in the Mediterranean population. There is increasing evidence that resveratrol exerts multifaceted antioxidant and/or anti-inflammatory effects in various disease models. Importantly, resveratrol was reported to slow aging and increase lifespan in simple organisms and has been suggested as a potential calorie restriction mimetic. Resveratrol has also been reported to activate NAD-dependent histone deacetylases (sirtuins), which may contribute to its anti-aging effects. This review focuses on the role of oxidative stress and inflammation in cardiovascular dysfunction in aging, and on emerging anti-aging therapeutic strategies offered by resveratrol and other polyphenol compounds.

The hydrogen sulfide signaling system: changes during aging and the benefits of caloric restriction

“…Caloric restriction (CR) is an intervention that attenuates many effects of aging (Anderson and Weindruch 2010;Labinskyy et al 2006;Leeuwenburgh and Prolla 2006), including cardiovascular morbidity (van der Loo et al 2000), cross-linking of cardiac and skeletal muscle proteins (Leeuwenburgh et al 1997), mitochondrial dysfunction (Aspnes et al 1997;Payne et al 2003), loss of skeletal muscle mass (Payne et al 2003;van der Loo et al 2000), and endothelial dysfunction (Barja 2002;Castello et al 2005;Gredilla et al 2004;Gredilla et al 2001;Taddei et al 2006). Furthermore, CR attenuates the age-related impairment of the NO signaling system (Minamiyama et al 2007;Sharifi et al 2008;Yang et al 2004).…”

Resveratrol increases vascular oxidative stress resistance

“…Resveratrol has been identified in more than 70 species of plants, including grapevines (Vitis vinifera), mulberries (Morus rubra), Vaccinum species, and peanuts (Arachis hypogea), and it is thought to have diverse antiatherogenic activities (42, 55-57, 60, 61), such as the inhibition of LDL oxidation (22) and platelet aggregation (46) and regulation of vascular smooth muscle proliferation (24 -26, 54). Recently, studies from this and other laboratories have shown that resveratrol inhibits endothelial activation and monocyte adhesion (12, 21, 39) and attenuates proinflammatory gene expression by inhibition of NF-B activation in coronary arterial endothelial cells (12).There is overwhelming evidence that oxidative stress plays a crucial role in the development of vascular disease and vascular aging (11,13,35). The mechanisms by which oxidative stress elicits endothelial cell injury during atherogenesis are likely to include induction of inflammatory processes (11) and activation of cellular apoptotic pathways (9).…”

“…There is overwhelming evidence that oxidative stress plays a crucial role in the development of vascular disease and vascular aging (11,13,35). The mechanisms by which oxidative stress elicits endothelial cell injury during atherogenesis are likely to include induction of inflammatory processes (11) and activation of cellular apoptotic pathways (9).…”

“…The mechanisms by which oxidative stress elicits endothelial cell injury during atherogenesis are likely to include induction of inflammatory processes (11) and activation of cellular apoptotic pathways (9). Although there is evidence for the inhibitory effect of resveratrol on oxidative stress-induced vascular inflammation (12,35), it is not well understood how resveratrol affects cellular resistance against proapoptotic effects of oxidative stressors. Recently, the view emerged that resveratrol may induce a dose-and cell type-dependent induction of both anti-and proapoptotic mechanisms (3,4).…”

Molecular Mechanisms of Cardiovascular Aging

“…This is in addition to increased scavenging of ROS, increased NO synthase activity, reduced platelet aggregation, angiogenesis activity and anti-apoptosis activity. (120)(121)(122)(123)(124)(125)(126)(127)(128)(129) As an example, SIRT1 regulates the activity of PGC-1a, a central factor in controlling energy state and contractile function in cardiac muscle. (130) SIRT1-induced angiogenic activity is probably mediated via FOXO transcription factors that regulate blood vessel endothelial development.…”