Daniel P. Kelly, M.D. (Director)

DEPARTMENT OF Internal Medicine
Keywords: cardiovascular disease, cardiovascular function, diabetes mellitus, clinical research

To decrease the morbidity and mortality of cardiovascular disease in patients with diabetes, we established a Specialized Center for Clinically Oriented Research (SCCOR) in cardiac function and disease. The central unifying theme of the SCCOR is to eliminate the excess burden of myocardial disease in people with diabetes. The program is designed to test the hypothesis that derangements in myocardial fatty acid metabolism leads to cardiac dysfunction and increased susceptibility to ischemic insult. We propose that metabolic (diabetes), genetic, racial and clinical determinants influence the outcome of patients at risk for an acute coronary ischemic event. The focus of this highly interactive center spans from fundamental studies of mouse models of the diabetic heart to outcomes studies in humans. Our approach combines molecular genetics, development and characterization of genetically modified mice, mechanism-based cardiovascular phenotyping in humans, and population outcomes research. We are examining the role of alterations in myocardial metabolism related to the PPARa gene regulatory pathway in response to ischemic insult in mouse models of the diabetic heart (Project 1); defining the role of myocardial lipotoxicity in the development of diabetic cardiac dysfunction in mice and humans (Project 2); delineating the contribution of increased myocardial fatty acid metabolism to pathologic ventricular remodeling in patients with diabetes mellitus following coronary ischemia/reperfusion or myocardial infarction using innovative metabolic imaging approaches (Project 3); investigating the basis of racial disparities, lipid metabolic derangements and genetic factors in outcomes following myocardial infarction (Project 4); and defining pharmacogenetic predictors of outcome in diabetic and non-diabetic patients following acute coronary syndrome (Project 5). The long-term objective of this SCCOR is to develop a rigorously defined risk-stratifying panel of imaging, biochemical, genetic and clinical determinants comprising a phenotypic profile of the patient with diabetes at risk for a cardiovascular event.