Mechanisms of Adiponectin-Associated Perivascular Function in Vascular Disease

Abstract

T hroughout the body, most arteries and veins with an internal diameter >100 μm are invested with a layer of perivascular adipose tissue (PVAT), which comprises adipocytes, inflammatory cells, and stem cells in phenotypic states that depend on the body mass of the individual and their premorbid state. Known locations of PVAT include the coronaries, aorta, and the microvascular beds of the mesentery, muscle, and kidney. [1][2][3][4][5] The fat cells were often regarded as mere repositories for excess energy and were removed before physiologists studied vascular structure and function. However, it is clear now that adipocytes are highly metabolically active and produce large numbers of substances that could influence the circulation both by paracrine and by endocrine effects. 6,7 This was demonstrated first by Soltis and Cassis,8 who reported a significantly reduced sensitivity to norepinephrine in segments of rat thoracic aorta surrounded by fat when compared with denuded vessels. Although this might be attributable to the barrier effect of the fat layer, and this is a contributory factor, 9 the effect could be corrected with desipramine plus deoxycorticosterone pretreatment implicating a sympathetic neuroeffector mechanism. Subsequently this so-called anticontractile effect of PVAT has been demonstrated in a variety of vascular beds from different species.10-14 The nature of the released adipokine(s) responsible is the subject of intense debate as are the mechanisms initiated and the picture is not complete: the vascular effects of PVAT vary depending on the anatomic location and in the case of the coronary vessels there are alternate effects on the endothelium and smooth muscle, 15,16 which are discussed in detail elsewhere in this review series. Please see http://atvb.ahajournals.org/site/misc/ ATVB_in_Focus.xhtml for all articles published in this series. Does PVAT Release Factors That Can Influence Vascular Tone?The simplest way to address this question is to stimulate a blood vessel surrounded with PVAT using a spasmogen in vitro and then expose a preconstricted artery denuded of PVAT to the organ bath solution. If there is a reduction in vascular reactivity or sensitivity, then this must be attributable to factor(s) released from PVAT. This approach has been applied to murine and human tissues, including mesenteric and subcutaneous gluteal arteries and aorta, and consistently there is an anticontractile response. [17][18][19] Furthermore, incubation and adrenergic stimulation of dissected PVAT alongside a denuded vessel further supports the secreted factor(s) hypothesis as opposed to physical blockade because vessels constrict significantly lesser than PVAT denuded counterparts. 10 What Is the Anticontractile Factor?Löhn et al 13 extended early studies and concluded that PVAT released a soluble factor that induces vasodilatation by opening smooth muscle K + channels. As a result of these reports, several candidates have been suggested as possible PVAT-mediated relaxing factors and include adiponectin, angi...

Perivascular Adipose Tissue, Potassium Channels, and Vascular Dysfunction

“…16 In contrast, recent studies in mesenteric vessels of wild-type mice advance that the vasorelaxing and hyperpolarizing effects of adiponectin rely on the opening of maxi Ca 2+ -activated K + (BK Ca ) channels. 28,29 In addition, a factor that might be adiponectin is released after stimulation of rat and murine mesenteric arteries with β3 adrenoreceptor. This latter factor seems to exert its paracrine effect by activation of AMPK and opening of BK ca channels.…”

Association Between C1q/TNF-Related Protein-1 Levels in Human Plasma and Epicardial Adipose Tissues and Congestive Heart Failure

“…Adipose tissue is an active endocrine organ that secretes a variety of molecules that affect both glucose metabolism and cardiovascular function [1]. Recently, epicardial adipose tissue (EAT) has emerged as a novel target for the stratification of cardiometabolic risk factors due to its unique location and multifaceted metabolic properties with systemic and local effects [2].…”

Similar Adiponectin Levels in Obese Normotensive and Obese Hypertensive Men and No Vasorelaxant Effect of Adiponectin on Human Arteries

“…Nevertheless, although numerous subsequent animal studies and in vitro experiments have reported that adiponectin has direct anti-inflammatory, anti-atherogenic, antihypertensive (vasodilatory) and antidiabetic (insulinsensitizing) properties [11][12][13][14], many human studies have failed to show any association between hypoadiponectinaemia and cardiovascular events [15][16][17], and the possibility that a low circulating amount of adiponectin is merely an innocent bystander rather than a genuine risk factor for obesity-related disorders certainly exists.…”

“…Another distinct feature is that adiponectin has been found to be inversely related to anthropometric measures, such as BMI and waist circumference [5,9,10], and to other metabolic factors found to be associated with higher risk of type 2 diabetes, CHD and hypertension, for example circulating insulin, glucose and triglyceride concentrations [4][5][6]9,10]. Furthermore, numerous animal studies have reported that adiponectin exerts direct anti-inflammatory, anti-atherogenic, antihypertensive (vasodilatory) and antidiabetic (insulinsensitizing) properties [11][12][13][14]. Nevertheless, even though adiponectin has been associated with well-known cardiovascular risk factors [4][5][6][8][9][10], a number of studies have failed to show any association between hypoadiponectinaemia and cardiovascular events in human beings, as summarized in three recent systematic reviews and meta-analyses [15][16][17].…”