Human Perivascular Adipose Tissue as a Regulator of the Vascular Microenvironment and Diseases of the Coronary Artery and Aorta

Abstract

Perivascular adipose tissue (PVAT) is an adipose depot that surrounds blood vessels in the human body and exerts local paracrine signaling. Under physiologically healthy conditions, PVAT has an anti-contractile effect on vessels, but in obesity this effect is lost. During metabolic disease, adiponectin secretion is dysregulated, influencing nitric oxide bioavailability and macrophage infiltration and inflammation, all of which mediate PVAT signaling. However, based on the location in the body, and the type of adipocyte present, PVAT has different relationships with risk factors for disease. Imaging studies in patients with cardiovascular disease have demonstrated important associations between PVAT structure and pathology, yet insight into molecular pathways regulating human PVAT function are still lacking. This review focuses on our current understanding of human PVAT and its secretory role in the vascular microenvironment. A current area of priority is defining molecular differences in the secretome between PVAT depots, as this could inform the treatment of diseases that occur in anatomically restricted locations. In addition, understanding progressive changes in PVAT structure and function during metabolic disease is required for effective targeted therapies.

Angiogenesis in adipose tissue and obesity

“…The defining feature of adipose tissue is the presence of adipocytes, which have the unique capacity to accumulate large amounts of lipid within specialized droplets, and give adipose depots their characteristic appearance. Despite a similar morphology, adipocytes comprise a heterogenous population of cells, and different types of adipocytes in each depot enable specialized functions [1][2][3]. For example, thermogenic adipocytes in adipose depots that surround central organs play a critical role in maintaining core body temperature.…”

“…In another example, subcutaneous adipose tissue (SqAT), the largest depot, is best able to expand in response to increased food intake. Other depots are more restricted in their ability to expand, and have other functions, including immunological surveillance by mesenteric adipose tissue [ 4 ], and regulation of vessel tone by perivascular adipose tissue [ 1 ]. The roles of other adipose tissue depots, such as those in the bone marrow, are still being defined [ 5 , 6 ].…”

Maternal Obesity Programming of Perivascular Adipose Tissue and Associated Immune Cells: An Understudied Area With Few Answers and Many Questions

“…Adipocytes are also capable of generating NO and hydrogen sulfide (H 2 S) directly which also contributes to vasorelaxation (Victorio et al, 2016;Xia et al, 2016;Donovan et al, 2018;Cacanyiova et al, 2019). This delicate balance is easily susceptible to disruption via dietary changes such as increased consumption of refined carbohydrates and saturated fats, which can facilitate phenotypic changes in the adipocyte and leukocyte populations which has been observed in both human and rodent arteries (Nosalski and Guzik, 2017;Stieber et al, 2019).…”

Perirenal Adipose Tissue—Current Knowledge and Future Opportunities

“…These fat deposits are physiologically involved in the maintenance of local and general homeostasis, via their endocrine and paracrine activity, but they may intervene in the pathogeny of some diseases. In this respect, the role of liver and muscle adipocytes in the development of diabetes mellitus [ 2 ], the intervention of epicardial fat in the development of atherosclerosis and ischemic coronary disease [ 3 ], and the involvement of perivascular adipose tissue (PVAT) in the pathogenesis of hypertension [ 4 ] have been recently identified.…”