Perivascular Adipose Tissue and Vascular Smooth Muscle Tone: Friends or Foes?

Abstract

Perivascular adipose tissue (PVAT) is a specialized type of adipose tissue that surrounds most mammalian blood vessels. PVAT is a metabolically active, endocrine organ capable of regulating blood vessel tone, endothelium function, vascular smooth muscle cell growth and proliferation, and contributing critically to cardiovascular disease onset and progression. In the context of vascular tone regulation, under physiological conditions, PVAT exerts a potent anticontractile effect by releasing a plethora of vasoactive substances, including NO, H₂S, H₂O₂, prostacyclin, palmitic acid methyl ester, angiotensin 1-7, adiponectin, leptin, and omentin. However, under certain pathophysiological conditions, PVAT exerts pro-contractile effects by decreasing the production of anticontractile and increasing that of pro-contractile factors, including superoxide anion, angiotensin II, catecholamines, prostaglandins, chemerin, resistin, and visfatin. The present review discusses the regulatory effect of PVAT on vascular tone and the factors involved. In this scenario, dissecting the precise role of PVAT is a prerequisite to the development of PVAT-targeted therapies.

Keywords: PVAT; anti-contractile; endothelial dysfunction; pro-contractile; vascular tone.

Figure 1

Blood vessels are made up of three cellular layers, namely intima (endothelial cells), media (VSMCs) and adventitia (fibroblast), and are surrounded by a fourth layer of adipose tissue called PVAT. PVAT is characterized by cellular heterogeneity harbouring adipocytes, endothelial and immune cells. PVAT regulates vascular tone via the secretion of vasoactive substances and adipokines. These factors, either anti-contractile or pro-contractile, decrease or increase the contractility of VSMCs, respectively. Ang 1-7, Angiotensin 1-7; PAME, palmitic acid methyl ester; PGI2, prostacyclin I₂; VMSC, vascular smooth muscle cell.

Figure 2

An overview of PVAT-derived anti-contractile factors and the mechanisms underpinning their effects. PVAT synthesizes several factors, including gases (NO and H₂S), small molecules (H₂O₂, PGI₂, and PAME) and proteins or peptides (adiponectin, angiotensin 1-7, leptin, and omentin). These factors act directly on VSMCs or indirectly on ECs through various mechanisms, such as activating K⁺ channels, soluble guanylyl cyclase, and prostacyclin I₂ receptors or by activating eNOS, ultimately reducing VSMC contraction. EC, endothelial cell; PVAT, perivascular adipose tissue; VSMC, vascular smooth muscle cell; AdpR1, adiponectin receptor 1; BK_Ca1.1, Ca²⁺-activated K⁺ channel; IP2, prostacyclin I₂ receptor; K_ATP, ATP-sensitive K⁺ channel; K_V, voltage-gated K⁺ channel; AC, adenylyl cyclase; CBS, cystathionine β-synthase; COMT, catechol-O-methyltransferase; CSE, cystathionine γ-lyase; e/nNOS; endothelial or neuronal nitric oxide synthase; PGI2S, PGI₂ synthase; sGC, soluble guanylyl cyclase; SOD, superoxide dismutase; Ang 1-7, angiotensin 1-7; Arg, arginine; Cys, cysteine; EDHF, endothelium-derived hyperpolarizing factor; NO, nitric oxide; PA, palmitic acid; PAME, palmitic acid methyl ester; PGH₂, prostaglandin H₂; PGI₂, prostacyclin I₂.

Figure 3

A synopsis of PVAT-derived contractile factors. PVAT synthesizes several factors and small molecules such as catecholamines and prostaglandins or peptides and proteins such as angiotensin II and chemerin. These factors act directly via different pathways on smooth muscle cells or indirectly by reducing the activity of eNOS, resulting in enhanced contractility of VSMCs. EC, endothelial cell; PVAT, perivascular adipose tissue; VSMC, vascular smooth muscle cell; αAR, α adrenergic receptor; AT1R, angiotensin II receptor type I; Ch23R, chemerin receptor 23; PGRs, prostaglandin receptors; ACE, angiotensin-converting enzyme; COX, cyclooxygenase; eNOS, endothelial nitric oxide synthase; NOX, NADPH oxidase; AC, arachidonic acid; Ang I, angiotensin I; Ang II, angiotensin II; CA, catecholamine; PGF2α, prostaglandin F2α; TXA, thromboxane A2.