Promotion of Cardiovascular Homeostasis by the Perivascular Adipose Tissue Secretome

Perivascular adipose tissue (PVAT) is a unique fat depot that is distributed around blood vessels, contiguous with the vascular adventitia. Due to this proximity, it serves as a local source of adipokines and vasoregulatory factors. Similar to other adipose depots, PVAT is responsive to changes in metabolic state and, at least in mice, can transition to a thermogenic adipocyte phenotype depending on metabolic health. Cardiovascular disease risk is highly correlated with metabolic health and increases substantially in individuals with obesity or metabolic syndrome. Cardiovascular diseases, including atherosclerosis/coronary artery disease, aortic aneurysm, hypertension, arterial stiffening, and heart failure, have been associated with PVAT dysregulation. Understanding the cardiovascular protective effects of healthy PVAT can provide ways to modify disease progression to re-establish functional homeostasis. This review focuses on experimental studies that specifically define a signaling axis between PVAT and the cardiovascular system that provide cardioprotection. Our focus is primarily on the secreted contents of extracellular vesicles that initiate this adipose signaling axis and regulation of extracellular vesicle release by the trafficking molecule, RAB27a. We review the current literature on human and mouse studies and major categories of PVAT-derived signaling components including microRNAs, lipids, and proteins that contribute to cardiovascular homeostasis.