Perivascular Adipose Tissue Angiotensin II Type 1 Receptor Promotes Vascular Inflammation and Aneurysm Formation

Abstract

Perivascular adipose tissue exhibits characteristics of active local inflammation, which contributes to the development of atherosclerotic disease as a complication of obesity/metabolic syndrome. However, the precise role of perivascular adipose tissue in the progression of abdominal aortic aneurysm remains unclear. To test the hypothesis that genetic deletion of angiotensin II type 1a (AT) receptor in perivascular visceral adipose tissue (VAT) can attenuate aortic aneurysm formation in apolipoprotein E-deficient (ApoE) mice, we performed adipose tissue transplantation experiments by using an angiotensin II-induced aneurysm murine model, in which we transplanted VAT from ApoE or ApoE AT donor mice onto the abdominal aorta of ApoE recipient mice. Compared with ApoE VAT transplantation, ApoE AT VAT transplantation markedly attenuated aortic aneurysm formation, macrophage infiltration, and gelatinolytic activity in the abdominal aorta. AT receptor activation led to the polarization of macrophages in perivascular VAT toward the proinflammatory phenotype. Moreover, osteopontin expression and gelatinolytic activity were considerably lower in ApoE AT perivascular VAT than in ApoE perivascular VAT, and angiotensin II-induced osteopontin secretion from adipocytes was eliminated after deletion of AT receptor in adipocytes. Notably, induction of macrophage migration by conditioned medium from angiotensin II-stimulated wild-type adipocytes was suppressed by treatment with an osteopontin-neutralizing antibody, and ApoE OPN VAT transplantation more potently attenuated aortic aneurysm formation than ApoE VAT transplantation. Our findings indicate a previously unrecognized effect of AT receptor in perivascular VAT on the pathogenesis of abdominal aortic aneurysm.

Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology

“…In addition, the role of perivascular visceral adipose tissue AT 1A R contributing to ANG II-induced AAA has been reported. Adipocyte-derived osteopontin via AT 1A R stimulation appears to contribute to AAA through inflammatory actions involving macrophage migration and polarization (902). Taken together, these studies highlight the roles of distinct cell type-specific signaling mechanisms by which ANG II may contribute to AAA development and the need for further investigation.…”

Perivascular adipose tissue (PVAT) in atherosclerosis: a double-edged sword

“…The AT1R is responsible for most biological effects of Ang II such as pressure, trophic, and pro-inflammatory effects. Sakaue et al reported that ATR1 receptor in PVAT promotes vascular inflammation and aneurysm formation [ 268 ]. Previous research has reported angiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEI) reduced PVAT inflammation, which is associated with the reduction of atherogenesis [ 269 ].…”

Decrease of Perivascular Adipose Tissue Browning Is Associated With Vascular Dysfunction in Spontaneous Hypertensive Rats During Aging

“…Perivascular adipose tissue (PVAT) is a structure surrounding most of the blood vessels, which plays vital roles in vascular physiopathology ( Brown et al, 2014 ). As an essential part of the vasculature, PVAT is involved in various vascular diseases, including atherosclerosis, aneurysm, and hypertension ( Takemori et al, 2007 ; Verhagen and Visseren, 2011 ; Sakaue et al, 2017 ). It is well established that adipose tissue includes brown adipose tissue (BAT) and white adipose tissue (WAT).…”