The Role of Perivascular Adipose Tissue in Atherosclerotic Cardiovascular Disease (PVAT-ASCVD)

Project Abstract Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of mortality in the United States, driven by systemic risk factors such as hyperlipidemia, hypertension, and diabetes. However, arteries show varying susceptibility to atherosclerosis, particularly the right coronary artery (RCA) and the left internal mammary artery (LIMA). The LIMA's resistance to atherosclerosis makes it the preferred graft in coronary artery bypass grafting (CABG) due to its long-term patency. Our research in human and mice perivascular adipose tissue (PVAT) has revealed that PVAT in different vascular regions exhibits distinct functional characteristics, particularly in terms of thermogenic capacity. This project aims to investigate the hypothesis that LIMA PVAT has a more thermogenic and anti-inflammatory phenotype compared to RCA PVAT, contributing to its resistance to atherosclerosis. In our proposal, the first aim is to characterize distinct adipocyte subtypes and intercellular signaling pathways within RCA and LIMA PVAT. The second aim is to explore the differentiation potential of PVAT progenitors and the adipocytes derived from PVAT in the RCA and LIMA. The third aim is to correlate thermogenic and anti- inflammatory transcriptomic profiles with imaging biomarkers of PVAT inflammation and atherosclerosis. Through these aims, we will uncover key molecular traits of PVAT that are important in the development of atherosclerosis. Understanding PVAT's influence on vascular homeostasis across vascular beds will lead to new therapies for diverse cardiovascular conditions, including coronary artery disease, peripheral artery disease and carotid artery disease.