Adipose-Vascular Coupling and Potential Therapeutics

Abstract

Excess visceral adipose tissue is associated with increased risk of high blood pressure, lipid disorders, type 2 diabetes, and cardiovascular disease. Adipose tissue is an endocrine organ with multiple humoral and metabolic roles in regulating whole-body physiology. However, perivascular adipose tissue (PVAT) also plays a functional role in regulating the contractile state of the underlying smooth muscle cell layer. Work during the past decade has shown that this adipose-vascular coupling is achieved by production of numerous substances released from PVAT. Animal disease models have been instrumental in identifying biological and pathophysiological functions of this regulation. These studies have produced strong evidence that alterations in the paracrine control of PVAT in the regulation of arterial tone contribute to vascular dysfunction in obesity, hypertension, and cardiometabolic disease. Perivascular relaxing factors, or perhaps their putative targets, might represent exciting new targets for the prevention and treatment of cardiovascular and metabolic diseases.

C1q/TNF‐related protein 9 improves the anti‐contractile effects of perivascular adipose tissue via the AMPK‐eNOS pathway in diet‐induced obese mice

“…Most studies have focused on the endothelial dysfunction, which significantly contributes to the initiation and progression of cardiovascular diseases . However, the importance of PVAT for modulation of the cardiovascular system has been recognized recently . PVAT is not only a special adipose tissue that surrounds most of the vasculature, but it is also considered as an active endocrine organ that secretes biological substances that modulate the vascular tone.…”

Perivascular adipose tissue and the dynamic regulation of Kv7 and Kir channels: Implications for resistant hypertension

“…However, mRNA of KCNQ2 was not detected in isolated smooth muscle cells from these arteries . Moreover, mRNA of KCNQ1, 3, 4, and 5 was detected in rat skeletal muscle arteries, suggesting that K v 7.1 and K v 7.3‐7.5 may be involved in regulation of vascular function (for details, see Ref …”

“…This vascular regulation depends on the anatomical integrity of the vessels and is mediated by a transferable “adipocyte‐derived relaxing factor” (ADRF) which opens smooth muscle K + channels . A few adipokines, notably adiponectin, angiotensin 1–7 (Ang1–7), H 2 O 2 , and methyl palmitate, have been suggested as potential perivascular relaxing factor (PVRF) candidates to explain the anticontractile properties of PVAT (for review, see Ref …”

Coronary artery hypoxic vasorelaxation is augmented by perivascular adipose tissue through a mechanism involving hydrogen sulphide and cystathionine‐β‐synthase

“…2,17 The present in situ experiments suggest that both PVAT and myocardium can attenuate the hypoxic contraction, and the replacement experiments identify the involvement of a diffusible factor. [6][7][8][9][10][11][12] In rat coronary arteries, cardiomyocyte-rich perivascular tissue had an anticontractile effect on agonist-induced contractions, which involved F I G U R E 8 Immunoblot analysis of porcine coronary artery, myocardium and perivascular adipose tissue (PVAT) (n = 4) shows expression of MPST (33 kDa) within the porcine coronary artery, myocardium and PVAT. The simplest explanation is that an anticontractile factor that is not H 2 S is involved in PVAT-mediated attenuation of hypoxic contraction of the coronary artery.…”

“…[6][7][8][9][10][11][12] We were interested in its contribution to vasomotor function during hypoxia in the heart because reduced oxygenation in ischaemia would be expected to affect the adjacent fat and the myocardium as well. [6][7][8][9][10][11][12] We were interested in its contribution to vasomotor function during hypoxia in the heart because reduced oxygenation in ischaemia would be expected to affect the adjacent fat and the myocardium as well.…”