Perivascular Adipose Tissue as a Relevant Fat Depot for Cardiovascular Risk in Obesity

Abstract

Obesity is associated with increased risk of premature death, morbidity, and mortality from several cardiovascular diseases (CVDs), including stroke, coronary heart disease (CHD), myocardial infarction, and congestive heart failure. However, this is not a straightforward relationship. Although several studies have substantiated that obesity confers an independent and additive risk of all-cause and cardiovascular death, there is significant variability in these associations, with some lean individuals developing diseases and others remaining healthy despite severe obesity, the so-called metabolically healthy obese. Part of this variability has been attributed to the heterogeneity in both the distribution of body fat and the intrinsic properties of adipose tissue depots, including developmental origin, adipogenic and proliferative capacity, glucose and lipid metabolism, hormonal control, thermogenic ability, and vascularization. In obesity, these depot-specific differences translate into specific fat distribution patterns, which are closely associated with differential cardiometabolic risks. The adventitial fat layer, also known as perivascular adipose tissue (PVAT), is of major importance. Similar to the visceral adipose tissue, PVAT has a pathophysiological role in CVDs. PVAT influences vascular homeostasis by releasing numerous vasoactive factors, cytokines, and adipokines, which can readily target the underlying smooth muscle cell layers, regulating the vascular tone, distribution of blood flow, as well as angiogenesis, inflammatory processes, and redox status. In this review, we summarize the current knowledge and discuss the role of PVAT within the scope of adipose tissue as a major contributing factor to obesity-associated cardiovascular risk. Relevant clinical studies documenting the relationship between PVAT dysfunction and CVD with a focus on potential mechanisms by which PVAT contributes to obesity-related CVDs are pointed out.

Sirtuin-1 and Its Relevance in Vascular Calcification

“…Perivascular adipose tissue (PVAT) is adipose tissue that surrounds large arteries and releases various factors, in paracrine or autocrine fashion, in the regulation of vascular function. PVAT has the ability to release proinflammatory adipokines or cytokines after insult and, consequently, promote inflammation, vasoconstriction, and VSMCs proliferation, which are all highly associated with cardiovascular risk, especially in obesity (Figure 2, yellow) [82]. Numerous studies have shown that PVAT plays a protective role against atherosclerosis by increasing the adiponectin level and eNOS expression, thereby inhibiting plaque formation, reducing inflammation, and improving endothelial function [83].…”

Perivascular adipose tissue in cardiovascular diseases – an update

“…Although it has been previously considered an inert component of the vascular wall, displaying a structural role, PVAT is currently seen as a key role tissue in vascular homeostasis and in the maintenance of the arterial tension (2).…”

“…The white adipose tissue (WAT), composed predominantly of cells exhibiting unilocular lipid inclusions, is mainly located in the hypodermis and perivisceral location. The brown adipose tissue (BAT), temporarily occurring in humans in the interscapular and mediastinal regions, is involved in the maintenance of a consistent body temperature, containing adipocytes with multiple cytoplasmic inclusions, of variable size, associated with a rich capillary network (1,2). The beige or brite (brown-in-white) adipose tissue (BeAT) may be disposed in between WAT cells and is able to develop a brown-like phenotype (1).…”

“…The interest regarding the origin and the involvement of this tissue in vascular homeostasis has been exponentially growing, as PVAT is currently considered more than a vascular tissue support, being an active contributor to vascular tonus regulation and a dual endocrine and paracrine organ, producing a panel of vasoactive and pro-inflammatory substances (2,5). The endocrine function is mainly performed by the release of adipokines into blood flow and their circulation to specific receptors.…”

“…The endocrine function is mainly performed by the release of adipokines into blood flow and their circulation to specific receptors. In contrast, the paracrine activity is characterized by a direct local release of vasoactive and pro-inflammatory substances, resulting in both insulin resistance (IR) and microvascular dysfunction (2,5).…”