Abstract 667: Aortic Remodeling in Angiotensin II Treated ACE2 Knockout Mice

Abstract

Angiotensin converting enzyme 2 (ACE2) is a protective regulatory protein that catalyzes conversion of Ang II to Ang-(1-7). There is much information on ACE2’s role in cardiac and renal pathologies, but limited data on ACE2 in vasculature. The objective was to study the role of ACE2 in the Ang II response as related to aortic remodeling and inflammation using ACE2 knockout (KO) mice. Eight week (C57Bl/6) male ACE2 KO and wild type (WT) mice (n= 7-8) were infused with Ang II (1000 ng/kg/min, 4 wks). Aortic structure (collagen, dimension), oxidative stress, and inflammatory cytokines were measured. Results showed a significant decrease ( p <0.05) in aortic luminal area in Ang II ACE2 KO over WT (74.51μm 2 /pixel vs. 91.50 μm 2 /pixel). Picrosirius red staining showed higher collagen in the outer aortic wall in Ang II infused ACE2 KO mice compared to Ang II WT (55% vs. 19%). Dihydroethidium (DHE) staining indicated marked elevation in superoxide generation following Ang II infusion in ACE2 KO (18%) compared to WT (7%). A BioPlex system was used to quantify a panel of 23 cytokines in aorta. It revealed higher macrophage inflammatory protein (MIP-1α) in Ang II ACE2 KO vs. Ang II WT mice (13.5 vs. 3.3 pg/ml). Two-way ANOVA showed a significant effect of treatment ( p < 0.02) for interleukin 1-α (IL-1α). Findings indicate that the aorta is a target site for Ang II’s pathological effects, an action which involves ACE2.