Arsenic Exposure, Endothelial Function and Platelet Activity in Type 2 Diabetes
Despite optimal medical therapy to reduce cardiovascular disease (CVD) risk, patients with type 2 diabetes (T2D) have a significantly greater risk of CVD than patients without T2D. Data from the prospective NIH/NHLBI Strong Heart Study suggested low to moderate inorganic arsenic exposure may be a novel risk factor for CVD, especially for patients with T2D. In the United States, exposure to inorganic arsenic at low to moderate levels is common, with millions of people exposed annually in the U.S. through food and drinking water. However, the mechanisms by which low to moderate arsenic exposure may increase CVD risk in patients with T2D have not been characterized. Therefore, our aims are to: (1) investigate whether increasing concentrations of glucose modify the effects of low to moderate concentrations of sodium arsenite on markers of human aortic and coronary endothelial cell dysfunction; and (2) investigate whether increasing concentrations of glucose modify the effects of low to moderate concentrations of sodium arsenite on platelet function and aggregability. This proposal will provide novel insights into the associations among low to moderate arsenic exposure, T2D, markers of endothelial dysfunction and platelet activity for the risk of CVD. These studies would be the first to examine in two model systems the effect of environmental modifiers such as arsenic exposure on the risk of CVD in T2D, and could be used to explore the risk of other environmental exposures as contributors to the excess risk of CVD in patients with T2D.

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