Abstract 525: Angiotensin Ii Type 1a Receptor Deletion In Vascular Smooth Muscle Cells Prevent Abdominal Aortic Aneurysm Formation Induced By Angiotensin Ii Plus β-aminopropionitrile

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 43; no. Suppl_1
• Main Authors: Okuno, Keisuke, Torimoto, Keiichi, Cicalese, Stephanie, Hashimoto, Tomoki N, Sparks, Matthew A, Rizzo, Victor J, Eguchi, Satoru
• Format: Journal Article
• Language: English
• Published: 01.05.2023
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/atvb.43.suppl_1.525

Abstract only Abdominal aortic aneurysm (AAA) is multifactorial disease resulting from changes in the aortic wall structure, such as medial degradation and inflammation, causing life-threatening AAA rupture. Angiotensin II (AngII) type 1A receptor (AT 1A R) upon AngII binding mediates blood pressure elevation and several chronic cardiovascular diseases including AAA. Treatment with AngII plus β-aminopropionitrile (BAPN), a lysyl oxidase inhibitor, in normolipidemic C57BL6 mice similarly induces AAA. However, we have limited understanding whether smooth muscle AT 1A R affects AAA formation induced by AngII plus BAPN. Thus, the subject of this study is to test the contribution of smooth muscle AT 1A R to AngII-dependent AAA development in normocholesterolemic mice. At 8 to 12 week of age, smooth muscle AT 1A R silenced mice (knock-in Tagln-Cre +/- crossed with AT 1A R flox/flox mice) and control mice were infused with AngII (1 μg/kg/min) via osmotic mini-pump for 4 weeks and treated with 1 g/L BAPN containing water for the first 2 weeks or sham-operated for mini-pump implantation. After 4 weeks, significant increases in maximum external aortic diameter and structural alterations were observed in the control mice, which was attenuated in smooth muscle AT 1A R silenced mice (1.67 mm vs. 1.22 mm, p<0.05). AngII plus BAPN treatment increased perivascular collagen III positive cell ratio, which was normalized in smooth muscle AT 1A R silenced mice (p<0.01). Evaluation of blood pressure at week 4 in conscious mice showed significant reduction in AngII-induced hypertension in smooth muscle AT 1A R silenced mice (p<0.01). Furthermore, in contrast to control mice, no death duet to aortic rupture was observed in smooth muscle AT 1A R silenced mice. In conclusion, our study has demonstrated the significant contribution of smooth muscle expressing AT 1A R in mediating AAA development and rupture in response to AngII plus BAPN treatment. It is possible that attenuation of hypertension in the AT 1A R silenced mice may provide additional protection against AAA rupture.