The influence of perivascular adipose tissue on vascular homeostasis

Abstract

The perivascular adipose tissue (PVAT) is now recognized as an active contributor to vascular function. Adipocytes and stromal cells contained within PVAT are a source of an ever-growing list of molecules with varied paracrine effects on the underlying smooth muscle and endothelial cells, including adipokines, cytokines, reactive oxygen species, and gaseous compounds. Their secretion is regulated by systemic or local cues and modulates complex processes, including vascular contraction and relaxation, smooth muscle cell proliferation and migration, and vascular inflammation. Recent evidence demonstrates that metabolic and cardiovascular diseases alter the morphological and secretory characteristics of PVAT, with notable consequences. In obesity and diabetes, the expanded PVAT contributes to vascular insulin resistance. PVAT-derived cytokines may influence key steps of atherogenesis. The physiological anticontractile effect of PVAT is severely diminished in hypertension. Above all, a common denominator of the PVAT dysfunction in all these conditions is the immune cell infiltration, which triggers the subsequent inflammation, oxidative stress, and hypoxic processes to promote vascular dysfunction. In this review, we discuss the currently known mechanisms by which the PVAT influences blood vessel function. The important discoveries in the study of PVAT that have been made in recent years need to be further advanced, to identify the mechanisms of the anticontractile effects of PVAT, to explore the vascular-bed and species differences in PVAT function, to understand the regulation of PVAT secretion of mediators, and finally, to uncover ways to ameliorate cardiovascular disease by targeting therapeutic approaches to PVAT.

Adipokines and cardiovascular disease: A comprehensive review

“…visfatin and resistin) (ref. 3,4 ). In response to vasoconstriction PVAT adipocytes react by the release of adipokines which induce anti-contractile effects on smooth muscle cells of adjacent blood vessels 5 .…”

Targeting endothelial metaflammation to counteract diabesity cardiovascular risk: Current and perspective therapeutic options

“…The differential role of regional fat depots in synthesis and release of specific mediators and vasoactive substances may help to reconcile the generally accepted 'outside-in' theory of vascular inflammation, which postulates that inflammation begins in adipose tissue and then spreads inward to the vasculature [87], with the 'inside-out' process of vascular inflammation, proposing that the first step is intimal injury, that then extends to the media and adventitia [88,89]. For example, it is plausible that intimate connections between perivascular adipose tissue (PVAT) and other components of the vessel wall result in PVAT being the first adipose depot to sense and respond to signals from circulating bioactive factors that influence activity of endothelial and vascular smooth muscle cells [90][91][92].…”

Perivascular adipose tissue: role in the pathogenesis of obesity, type 2 diabetes mellitus and cardiovascular pathology.

“…Однако соотношение и взаимодействие их в периваскулярной жировой ткани при сердечно-сосудистых заболеваниях остается до конца неясным [27,28].…”

“…В периваскулярной жировой ткани вырабатываются вещества, которые не секретируются другой жировой тканью -например, так называемый фактор роста гепатоцитов. Медиатор способствует пролиферации эндотелия и высвобож-дению цитокинов из гладкомышечных клеток [27]. Продукция фактора роста гепатоцитов в периваску-лярной жировой ткани повышается при ожирении.…”