Dual Modulation of Vascular Function by Perivascular Adipose Tissue and Its Potential Correlation with Adiposity/Lipoatrophy-Related Vascular Dysfunction

Yu-Jing Gao

Abstract

Almost every systemic vessel is surrounded by a layer of perivascular adipose tissue (PVAT), which had been mainly considered as a mechanical support for vasculature. However, recent advances have revealed that PVAT is an active player in controlling vessel function. PVAT releases relaxation factor(s) with unknown chemical identity (named perivascular adipocyte-derived relaxation factor, PVRF) that attenuates vasoconstriction to various agonists including phenylephrine, serotonin, angiotensin II, and U 46619 (a thromboxane A2 mimic), through activation of K+ channels. PVAT also promotes vasoconstriction to perivascular nerve stimulation by producing vasoconstrictor or facilitator (named perivascular adipocyte-derived constricting factor, PVCF), which includes superoxide and was mediated through activation of tyrosine kinase and MAPK/ERK pathways. Therefore, PVAT has a dual regulatory role in modulating vessel function, attenuating vasoconstriction to agonists by PVRF and promoting constriction to perivascular nerve excitation by PVCF. In vivo, normal amount of PVAT (total body fat as well) is likely to be important in maintaining the homeostasis of vascular tone and blood pressure, since lipoatrophic mice developed hypertension. On the other end, excessive accumulation of body fat (obesity) impaired PVRF production/action, despite an increase in the amount of PVAT. In spontaneously hypertensive rats, an animal model of hypertension without obesity, the ability of PVAT to attenuate vasoconstriction to agonists was reduced, and treatment with atorvastatin improved PVAT function. PVAT, vasodilating and constricting factors of PVAT origin, and signalling pathways of these factors may represent new targets for developing new strategies to treat vascular disorders associated with abnormal adiposity.

Keywords: Adiposity, artery, contraction, hypertension, perivascular adipose tissue, relaxation

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