The goal of this Specialized Center of Research (SCOR) for Ischemic Heart Disease in Blacks is to elucidate the pathophysiological basis for excess morbidity and mortality from ischemic heart disease in African-American persons with diabetes mellitus, and to develop effective countermeasures to address this problem. The SCOR will be comprised of 8 research units and 3 core units. Investigations will range from fundamental studies of disease mechanisms to clinical research designed to influence medical practice in the near term. Research unit I, """"""""Coronary flow and myocardial supply/demand relationships in blacks with NIDDM"""""""", will test the hypothesis that abnormalities in coronary reactivity in black diabetics are reversible, at least in part, by interventions that increase insulin sensitivity and ameliorate the metabolic perturbations associated with NIDDM. Research unit II, """"""""Genotyping for risk stratification"""""""", will examine the importance of the ACE gene for manifestations of ischemic heart disease in blacks using a novel application of shared allele analysis in large families. Research unit III, """"""""Reflex control of the peripheral circulation in NIDDM"""""""", will define mechanisms by which insulin resistance modulates the reflex neurogenic control of the skeletal muscle circulation and contributes to hypertension and LVH in blacks. Research unit IV, """"""""Protection of the ischemic myocardium by hsp70"""""""" will elucidate mechanisms of the cytoprotective function of hsp70 within the ischemic heart. Research unit V, """"""""alpha B-crystallin/small HSP in the diabetic heart"""""""", will test the hypothesis that small hsps act alone, and/or synergistically with hsp70, to delay the onset and progression of irreversible injury within the ischemic myocardium. Research unit VI, """"""""Hyperlipacidemia in the pathogenesis of diabetic cardiomyopathy"""""""", will examine the role of elevated free fatty acids in exacerbating ischemic injury in the diabetic heart. Research unit VII, """"""""Genetic modification of lipoprotein metabolism in obesity/insulin resistance"""""""", will assess the feasibility of correcting abnormalities in glucose clearance and fatty acid oxidation by hepatic gene transfer in an animal model of type II diabetes. Research unit VIII, """"""""Genetic modification of lipoprotein metabolism in obesity/insulin resistance"""""""", will employ somatic cell gene transfer methods to modify cholesterol metabolism in animal models to correct the atherogenic lipoprotein profile associated with diabetes. Core units for Administration, Biotechnology, and Histopathology will support and expand the activities of the research units. Research conducted within this SCOR seeks to improve medical therapy of ischemic heart disease, and to promote the overall mission of the National Heart, Lung and Blood Institute in reducing human suffering and death attributable to cardiovascular disorders.
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