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.

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Objective: Extracellular matrix (ECM) regulates various cellular functions as well as provides structural support. SPARC (secreted protein acidic and rich in cysteine) is one of the ECM components, which participates in various cellular functions, especially during morphogenesis and tissue remodeling. We have reported that 1) SPARC, which increases in accordance with renal injury, causes collagen deposition through ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin type 1 motif) production, and 2) renin-angiotensin system is placed in the upstream of SPARC overexpression in the hypertensive rat kidney. The present study investigated the roles for SPARC in vascular endothelial cell dysfunction and inflammation in the setting of hypertension.Design and method: Rats were treated with deoxycorticosterone acetate (DOCA) and 1% salt water for 0, 1, 2 or 3 weeks. Blood pressure was measured by tailcuff methods, and thoracic aorta was isolated to examine acetylcholine-induced vasodilatory response, macrophage infiltration by immunohistochemistry, and protein expression of SPARC and ADAMTS1 by Western blotting. In the separate experiment, angiotensin II (10 -7 mol/L, 6hr) or SPARC recombinant protein (100nmol/L, 24hr) was treated to cultured rat aortic endothelial cells (RAECs) with/without siRNA targeting SPARC and ADAMTS1. MCP-1 and LOX-1 mRNA levels were measured by real-time RT-PCR.Result: DOCA-salt caused time-dependent increases in systolic blood pressure, impairment of endothelium-dependent vasodilation, and macrophage infiltration into the adventitial area of the aorta. The expression of SPARC in the DOCAsalt rat aorta was enhanced at week1 and week2 compared to week0. ADAMTS1 expression tended to increase from week1 and showed significant increases at week3. In RAECs, SPARC and ADAMTS1 gene knockdown aggravated angiotensin II-induced overexpression of LOX-1 and MCP-1 mRNA, indicating antiinflammatory effects of SPARC. On the other hand, SPARC recombinant protein treatment induced the upregulation of LOX-1 and MCP-1.Conclusions: SPARC may be induced at the early stage of vascular injury to compensate inflammation under the existence of angiotensin II. We need further investigation into the diverse effects of SPARC and the relationship between SPARC and ADAMTS1.