The goal of this research proposal is to investigate the effect of plasma homocysteine concentrations on changes in the circulating concentrations of cellular fibronectin (CFN), a marker of endothelial dysfunction. Increased concentrations of plasma homocysteine have been found to be a strong independent risk factor for stroke, coronary and peripheral vascular disease. The mechanism by which increased plasma homocysteine promotes vascular disease is unknown, however homocysteine is thought to exert a direct cytotoxic effect upon the function of endothelial cells. Plasma homocysteine concentrations from fasting individuals have been found to correlate strongly with CFN, a marker of endothelial dysfunction. These results have led to following hypothesis: Homocysteine has an effect upon endothelial cell function that leads to an increased release of cellular fibronectin as a marker of endothelial dysfunction.
The specific aim i s to demonstrate whether increases in plasma homocysteine concentrations are associated with endothelial cell function as assessed by increases in the release of cellular fibronectin.
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