The Role of Highly inflamed Epicardial Adipose Tissue in the Development of Atrial Fibrillation

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Project Abstract My long-term goal is to be a clinical-translational research scientist focused on developing effective therapies for patients with cardiovascular disease. My background in the development and physiology of adipose tissue as well as clinical training in cardiovascular medicine have motivated me to better understand the molecular mechanisms by which epicardial adipocytes influence the development of atrial fibrillation. I propose to conduct a prospective clinical investigation to test the hypothesis that adipocytes are recruiting myeloid cells to the myocardium to increase vulnerability for postoperative AF. The specific aims of my proposal are: Aim 1. Characterize transcriptomic profiles of epicardial adipocytes and determine circulating levels of adipose-derived chemokines Aim 2. Determine the relationship between inflammation in epicardial adipose tissue and left atrial function as assessed by echocardiographic parameters, including left atrial volume index, left atrial function index and left atrial mechanical dispersion. Aim 3. Examine the relationship between inflammation in epicardial adipose tissue and incident postoperative AF after coronary artery bypass graft surgery I am seeking a K23 Mentored Patient-Oriented Career Development Award from the National Heart Lung and Blood Institute allow me the opportunities to expand my skills in clinical research methodologies, bioinformatics and biostatistics and enable me to be a translational scientist. The training plan in this proposal takes advantage of coursework and a strong mentoring team (Drs. McManus, Fitzgerald, and Corvera) with broad expertise (atrial fibrillation, innate immunity, adipocyte biology and clinical research methodologies) to fill key gaps in my previous training to advance my career goals. This proposal is among the first to explore the mechanism by which myeloid cells are recruited to the myocardium. This work will provide novel insights into the association between epicardial adipose tissue, inflammation and postoperative AF. The recruitment of inflammatory cells is key to the subsequent immune-mediated dysregulation of the electrical properties in cardiomyocytes and the downstream fibrotic processes. Understanding the molecular mediators of inflammation will identify new treatments for postoperative AF.