Angiotensin generation profile in the aorta of mice and patients with abdominal aortic aneurysm (AAA)

• Grant number: 22/13048-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2022
• End date: September 30, 2023
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Christiane Becari
• Grantee: Daniely Franco Francisco
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 17/21539-6 - Role of renin angiotensin system in Abdominal Aortic Aneurysm, AP.JP

Abstract

The renin-angiotensin system (RAS) is involved in physiological and pathological processes. Currently, a new paradigm has emerged where two main axes are believed to modulate SRA function: a deleterious axis composed of ACE/Ang II/AT1 receptor, and another beneficial axis composed of ACE2/Ang-(1-7)/MAS receptor. These functional aspects increase the range of possible targets for the treatment of cardiovascular diseases, including abdominal aortic aneurysms (AAA). Experimental research in mice and rats indicates an important contribution of RAS in the pathogenesis of AAA. An experimental model of AAA formation is through the chronic infusion of Ang II in mice. This aneurysm model mimics the disease seen in humans with several similar features. Thus, in the present IC-4 project we intend to carry out the biochemical characterization of the RAS components. The biochemical characterization will be performed by analyzing the proteolytic profile of enzymes that contribute to the formation and degradation of Ang II, Ang 1-7, and Ang IV from Ang I in aortic homogenate obtained from control mice and mice with AAA and patients with and without aneurysm, using specific substrates and inhibitors of the RAS. We will perform the analysis of the proteolytic profile of the different angiotensins by mass spectrometry. In addition, we will continue with the translational analysis of ACE, ACE-2, and renin, through the ELISA assay, in patients with AAA and control patients.In these projects present we proposed the experimental groups: I) Mouse C57Bl/6 Control; II) Knockout Mouse She-2 Control; III) C57Bl/6 mice with AAA; IV) Knockout mice Ela-2 with AAA. And for the Clinical Part: I) aorta from patients with AAA and II) aorta from control patients.The innovation and importance of the present project consist of the analysis of the proteolytic profile of formation and degradation of angiotensins in a translational way in the pathophysiology of abdominal aortic aneurysms.