PR000387 (Project)

Description:Age is the major risk factor for cardiovascular diseases (CVD). Two key contributors to the increased risk of CVD in middle-aged and older (MA/O) adults are stiffening of the large elastic arteries and the development of vascular endothelial dysfunction, indicated by impaired nitric oxide (NO)-induced endothelium-dependent dilation (EDD). The mechanisms by which aging causes arterial dysfunction are incompletely understood, but involve reductions in NO bioavailability associated with the development of oxidative stress and inflammation. Thus, establishing novel strategies to reduce arterial stiffness and increase vascular endothelial function in MA/O adults by increasing NO bioavailability and reducing oxidative stress and inflammation are a high biomedical research priority. Curcumin is a naturally occurring phenol found in the Indian spice turmeric that improves physiological function in animal models of age-related diseases and is a promising nutraceutical for intervention for promoting healthy aging. Our preclinical results indicate that chow supplemented with curcumin reduces aortic pulse wave velocity (PWV), the most common and clinically important measure of large elastic artery stiffness, restores NO-mediated EDD and reduces arterial oxidative stress and inflammation in old C57/BL6 mice. Preliminary data from our recently funded NIH R21 pilot grant indicate that curcumin supplementation improves vascular function in humans. It is possible that changes in the circulating (plasma) metabolome with oral curcumin supplementation will provide insight into novel metabolic mechanisms by which curcumin may improve vascular function. The goal of this project is to identify key metabolic pathways that change with oral curcumin supplementation and to relate those changes with improvements in vascular function in MA/O adults with initial endothelial dysfunction. Metabolomic analysis of plasma samples at baseline also may produce unique molecular signatures that predict responsiveness (changes in vascular function) to curcumin supplementation among individuals.