Perivascular adipose tissue inflammation in vascular disease

Abstract

Perivascular adipose tissue (PVAT) plays a critical role in the pathogenesis of cardiovascular disease. In vascular pathologies, perivascular adipose tissue increases in volume and becomes dysfunctional, with altered cellular composition and molecular characteristics. PVAT dysfunction is characterized by its inflammatory character, oxidative stress, diminished production of vasoprotective adipocyte-derived relaxing factors and increased production of paracrine factors such as resistin, leptin, cytokines (IL-6 and TNF-α) and chemokines [RANTES (CCL5) and MCP-1 (CCL2)]. These adipocyte-derived factors initiate and orchestrate inflammatory cell infiltration including primarily T cells, macrophages, dendritic cells, B cells and NK cells. Protective factors such as adiponectin can reduce NADPH oxidase superoxide production and increase NO bioavailability in the vessel wall, while inflammation (e.g. IFN-γ or IL-17) induces vascular oxidases and eNOS dysfunction in the endothelium, vascular smooth muscle cells and adventitial fibroblasts. All of these events link the dysfunctional perivascular fat to vascular dysfunction. These mechanisms are important in the context of a number of cardiovascular disorders including atherosclerosis, hypertension, diabetes and obesity. Inflammatory changes in PVAT's molecular and cellular responses are uniquely different from classical visceral or subcutaneous adipose tissue or from adventitia, emphasizing the unique structural and functional features of this adipose tissue compartment. Therefore, it is essential to develop techniques for monitoring the characteristics of PVAT and assessing its inflammation. This will lead to a better understanding of the early stages of vascular pathologies and the development of new therapeutic strategies focusing on perivascular adipose tissue.

Oxidative Stress, Inflammation, and Vascular Aging in Hypertension

“…17,[67][68][69][70] Oxidative stress is central in the pathology both as an initiator of vascular and renal inflammation and the consequence of inflammatory responses and cytokines. [71][72][73] This is particularly important, in light of the role of immunosenescent T cells in hypertension and the susceptibility of T cells to changes associated with aging.…”

“…16 It also promotes recruitment of inflammatory cells into the vascular wall to promote vascular disease. 17 In contrast, BMP7 attenuates left ventricular remodeling under pressure overload. 18 The importance of BMP in vascular and cardiac damage in hypertension is further supported by studies demonstrating that BMP inhibition attenuates vascular inflammation and calcification.…”

“…18 The importance of BMP in vascular and cardiac damage in hypertension is further supported by studies demonstrating that BMP inhibition attenuates vascular inflammation and calcification. 17 Vascular stiffening occurring with age is a good example of the interplay between oxidative stress and inflammation. 19,20 Both of these processes increase with aging.…”

Gestational intermittent hypoxia induces endothelial dysfunction, reduces perivascular adiponectin and causes epigenetic changes in adult male offspring

“…Perivascular adipose tissue (PVAT) modulates vascular reactivity through the secretion of bioactive molecules such as adiponectin (Xia & Li, ). Inflammation diminishes the anti‐contractility effects of PVAT (Nosalski & Guzik, ) and also reduces adiponectin secretion (Almabrouk et al . ) in mice.…”

Rab27a Regulates Human Perivascular Adipose Progenitor Cell Differentiation

“…PVAT modulates vascular and metabolic function by paracrine secretion of growth factors and adipokines in the local environment [34–36]. We searched for candidate secretory proteins enriched in PVAT compared to subcutaneous white adipose tissue (WAT) by MS/MS of whole tissue lysates.…”