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 (AT1a) 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-/- AT1a-/- donor mice onto the abdominal aorta of ApoE-/- recipient mice. Compared with ApoE-/- VAT transplantation, ApoE-/- AT1a-/- VAT transplantation markedly attenuated aortic aneurysm formation, macrophage infiltration, and gelatinolytic activity in the abdominal aorta. AT1a 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-/- AT1a-/- perivascular VAT than in ApoE-/- perivascular VAT, and angiotensin II-induced osteopontin secretion from adipocytes was eliminated after deletion of AT1a 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 AT1a receptor in perivascular VAT on the pathogenesis of abdominal aortic aneurysm.

DOI: 10.1161/HYPERTENSIONAHA.117.09512

Cite this paper

@article{Sakaue2017PerivascularAT, title={Perivascular Adipose Tissue Angiotensin II Type 1 Receptor Promotes Vascular Inflammation and Aneurysm Formation.}, author={Tomoki Sakaue and Jun -Ichi Suzuki and Mika Hamaguchi and Chika Suehiro and Akiko Tanino and Tomoaki Nagao and Teruyoshi Uetani and Jun Aono and Hirotomo Nakaoka and Mie Kurata and Tomohisa Sakaue and Takafumi Okura and Takumi Yasugi and Hironori Izutani and Jitsuo Higaki and Shuntaro Ikeda}, journal={Hypertension}, year={2017}, volume={70 4}, pages={780-789} }