The objective of this revised application is to create a Center of Biomedical Research Excellence in Obesity and Cardiovascular Disease (COCVD) to identify mechanisms linking the epidemic of obesity to the high incidence of cardiovascular diseases in the obese population, and to use this focus as a platform to develop promising junior investigators and enhance their success at competing for NIH grant support. We will achieve this objective by (1) assembling a group of established extramurally-funded scientists who will mentor faculty serving as principal investigators on research projects that address timely and significant questions related to obesity and cardiovascular disease, (2) providing a variety of mentoring approaches that will facilitate the development of research projects by investigators, leading to independent NIH-funded research, (3) developing and supporting shared use core facilities that support and extend research methods critical to the study of obesity and cardiovascular disease, (4) providing pilot grants for new projects focused on obesity and cardiovascular diseases, (5) facilitating symposia, seminars and meetings of participants researching obesity and cardiovascular diseases, (6) focusing on the research of the center at retreats dedicated to evaluating progress by investigators studying obesity and cardiovascular diseases, (7) strategically hiring promising new faculty to develop a critical mass of productive physician and basic scientists studying obesity and cardiovascular diseases. Five investigators, representing both physician and basic scientists, will serve as principal investigators on research projects that address a central hypothesis and that utilize a common model of diet-induced obesity to study obesity-induced hypertension, atherosclerosis, and platelet dysfunction/vascular inflammation. The central hypothesis of this revised proposal is that obesity induces changes in the production and release of adiopkines and other inflammatory mediators to promote cardiovascular diseases. Each project addresses aspects of this hypothesis using a common model of diet-induced obesity, and the projects synergize through their focus on adipokines, inflammation and through coordinate development of multiple cardiovascular diseases. The proposed structure and mentoring mechanisms will meet the need of increasing NIH funded research, and will develop a multi-disciplinary Center around the clinically significant area of obesity and cardiovascular disease.
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