The overall hypotheses of the Cardiovascular Complications and Diabetes Program Project are that (i) dysfunctional HDL increases the risk of cardiovascular disease in diabetes and the metabolic syndrome, and (ii) the increased glucose, triglycerides and systemic inflammation that characterize diabetes and the metabolic syndrome reduce HDL's cardio protective properties. We propose that the increased risk of cardiovascular disease (CVD) associated with these disorders can be understood, prevented, and treated only by increasing our knowledge of the factors that regulate HDL function and macrophage and adipocyte inflammatory phenotypes. HDL's contribution to CVD associated with diabetes and the metabolic syndrome has been largely overlooked, and we believe that a highly interactive and interdisciplinary group of investigators with extensive expertise in this area, such as ours, i needed to answer this question. The expertise of our team in different aspects pertaining to the overall hypotheses of this Program Project will ensure synergy and cross-fertilization between Projects, which is likely to markedly advance research in this important and timely area. The Program Project Grant consists of four Projects and three Core units: * Project 1: HDL Function and Oxidation in Diabetic Atherosclerosis - Jay W. Heinecke, MD, Project Leader * Project 2: Dyslipidemia and Atherosclerosis Regression - Ira J. Goldberg, MD, Project Leader and Edward A. Fisher, MD, PhD, Co-Investigator * Project 3: Adipose Tissue Inflammation and HDL Function - Alan Chait, MD, Project Leader * Project 4: Diabetes-induced Myeloid Cell Activation, HDL and Atherosclerosis - Karin E. Bornfeldt, PhD, Project Leader * Core A: Administrative Core - Karin E. Bornfeldt, PhD, Core Director, Alan Chait, MD, Co-Director * Core B: Quantitative and Functional HDL Core - Tomas Vaisar, PhD, Core Director * Core C: Tissue and Imaging Core - Kevin D. O'Brien, MD, Core Director
The proposed studies will have important implications for the management of patients with diabetes and the metabolic syndrome, in whom the risk of premature cardiovascular disease remains a serious threat. The investigations will provide important and interrelated insights into biomarkers and fundamental mechanisms of diabetic vascular disease, which in the long-term will set the stage for the development of new therapeutic agents and pharmacological strategies designed to interrupt the devastating complications of diabetes.
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