Abstract P109: Angiotensin 1-7 Attenuates Angiotensin II-induced Aortic Aneurysm In A Preclinical Murine Model

Background: Aortic aneurysm (AA) is a vascular disease that involves extracellular matrix degeneration of the aorta wall leading to dilatation and eventually aorta wall rupture. Aortic aneurysms contribute significantly to global morbidity and mortality due to vascular diseases. Elusive pathophysiology of initiation and progression of aortic aneurysm led to the absence of clinically relevant therapeutic interventions against aortic aneurysm. Though the role of AngII in the development and progression of AA is widely studied, the effect of Ang 1-7 on hallmarks of AA i.e. SMCs apoptosis, aorta matrix remodeling, and inflammation are poorly understood. Methods and Results: In the present study, we have investigated Ang 1-7-mediated protective effect on the AngII-infused murine model. AngII-infused ApoEKO murine model showed aortic dilatation in the thoracic and abdominal region with matrix remodeling. Infusion of Ang 1-7 rescued the phenotype evident by echocardiography. While histology staining showed excessive matrix remodeling i.e. collagen deposition in thoracic aorta and immunofluorescence showed VSMCs cell death in the abdominal aorta, suggesting different mechanisms underlying the development of TAA and AAA. The inflammatory markers, MMP2, MMP9, and TNF-α were significantly reduced in the thoracic aorta post-infusion of Ang 1-7. The Ang 1-7 treatment led to a reduced phenotypic switch in abdominal VSMCs evident by increased expression of ACTA2, MyH11, Calponin and reduced expressions of MMP2, MMP9, Collagen I, and collagen III. The apoptosis assay using flow cytometry showed attenuation of cell death of abdominal VSMCs after infusion of Ang 1-7 in a murine model of AA. The analysis of apoptosis-associated proteins, Caspase 3 and 8, showed reduced expression in the abdominal aorta. Conclusion: The study showed mitigation of AngII-mediated AA by Ang 1-7 infusion. Ang 1-7 treatment attenuated AngII-induced TAA by suppressing aortic matrix remodeling and AAA by inhibiting VSMCs apoptosis and vascular inflammation. Ang 1-7 can be a potential therapeutic alternative for the treatment of AA.