Inhibition of smooth muscle cell death by Angiotensin 1-7 protects against abdominal aortic aneurysm

Biosci Rep. 2023 Nov 10:BSR20230718. doi: 10.1042/BSR20230718. Online ahead of print.ABSTRACTAbdominal aortic aneurysm (AAA) represents a debilitating vascular disease characterized by aortic dilatation and wall rupture if it remains untreated. We aimed to determine the effects of Ang 1-7 in a murine model of AAA and to investigate the molecular mechanisms involved. 8-10 weeks old apolipoprotein E-deficient mice (ApoEKO) were infused with Ang II (1.44 mg/kg/day, s.c.) and treated with Ang 1-7 (0.576 mg/kg/day, i.p.). Echocardiographic and histological analyses showed abdominal aortic dilatation and extracellular matrix remodeling in Ang II-infused mice. Treatment with Ang 1-7 led to suppression of Ang II-induced aortic dilatation in the abdominal aorta. The immunofluorescence imaging exhibited reduced smooth muscle cell (SMC) density in the abdominal aorta. The abdominal aortic SMCs from ApoEKO mice exhibited markedly increased apoptosis in response to Ang II. Ang 1-7 attenuated cell death, as evident by increased SMC density in the aorta and reduced annexin V/propidium iodide-positive cells in flow cytometric analysis. Gene expression analysis for contractile and synthetic phenotypes of abdominal SMCs showed preservation of contractile phenotype by Ang 1-7 treatment. Molecular analyses identified increased mitochondrial fission, elevated cellular and mitochondrial reactive oxygen species (ROS) levels, and apoptosis-associated proteins, including Cytochrome C, in Ang II-treat...

Source: Bioscience Reports - November 10, 2023 Category: Biomedical Science Authors: Anshul S Jadli Karina P Gomes Noura N Ballasy Tishani Methsala Wijesuriya Darrell Belke Paul W M Fedak Vaibhav B Patel Source Type: research