Abstract 16792: Deletion of Angiotensin II Type 1a Receptor in Perivascular Adipose Tissue Attenuates Abdominal Aortic Aneurysm in Apolipoprotein E-/- Mice
Introduction: Perivascular adipose tissue (PVAT) exhibits features characteristic of active local inflammation, which contributes to the development of atherosclerotic disease as a complication of obesity/metabolic syndrome. In this study, we investigated the role of PVAT in the progression of abdominal aortic aneurysm (AAA) and hypothesized that deletion of angiotensin II (Ang II) type 1a (AT1a) receptor in PVAT could attenuate AAA in apolipoprotein E-deficient (ApoE-/-) mice.
Methods and Results: We performed adipose tissue transplantation experiments using an Ang II-induced aneurysm murine model to assess the role PVAT in AAA. Epididymal fat pads from ApoE-/- or ApoE-/-AT1a-/- donor mice were transplanted onto abdominal aorta of ApoE-/- or ApoE-/-AT1a-/- recipient mice fed a high-fat diet. AAA was induced in the adipose tissue transplanted mice by infusing 1,000 ng/kg/min Ang II for 4 weeks. ApoE-/-AT1a-/- PVAT transplantation significantly attenuated AAA in ApoE-/- recipient mice compared to ApoE-/- PVAT-transplanted ApoE-/- recipient mice. On the other hand, ApoE-/- PVAT transplantation significantly exacerbated AAA in ApoE-/-AT1a-/- recipient mice compared to ApoE-/-AT1a-/- PVAT-transplanted ApoE-/-AT1a-/- recipient mice. Accumulation of macrophages and expression of inflammatory cytokines was attenuated in ApoE-/-AT1a-/- donor PVAT compared to ApoE-/- donor PVAT. Fluorescence activated cell sorting analysis revealed that the macrophages in ApoE-/- adipose tissue were polarized towards the pro-inflammatory M1 phenotype. Moreover, expression of osteopontin and the activity of matrix metalloprotease (MMP)-2, 9 were attenuated in ApoE-/-AT1a-/- donor PVAT compared to ApoE-/- donor PVAT.
Conclusions: Deletion of AT1a receptor in PVAT attenuates AAA by inhibiting both inflammation and MMP activity. Our results seem to indicate a previously unrecognized role for the AT1a receptor of PVAT in the development and progression of AAA.
Author Disclosures: T. Sakaue: None. J. Suzuki: None. C. Suehiro: None. T. Uetani: None. J. Aono: None. T. Okura: None. J. Higaki: None. S. Ikeda: None.
- © 2016 by American Heart Association, Inc.