Renin-angiotensin system molecular analyses an in the development of in the Ang-II induced aneurysm in mice

• Grant number: 19/24369-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2020
• End date: December 31, 2020
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Christiane Becari
• Grantee: Carolina D'Avila Mesquita
• 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. Nowadays, a new paradigm has emerged in which it is believed that two central axes modulate the function of the RAS: a deleterious axis composed of ACE/Ang II/AT1 receptor and another beneficial axis formed of ACE2/ Ang 1-7/MAS receptor. These functional aspects multiply the possible treatment targets for the treatment of cardiovascular diseases, including the abdominal aortic aneurysm (AAA). Experimental researches in mouse and rats indicate critical participation of the RAS in the pathogenesis of the AAA. An experimental model of formation of the AAA is through the chronic infusion of AngII in mice. This model of aneurysm simulates human disease in many aspects. Thus, we plan to induce AAA in C57B1/6 mice and investigate the AAA produced modifications in the components of RAS system (angiotensinogen, renin, aminopeptidases, carboxypeptidases, chymase, elastase-2, ACE, ACE-2, AT1R, AT2R, AT4R and MASR). Furthermore, we ought to describe the formation of Ang II, Ang 1-7 and Ang Vi from AngI, in the presence and absence of specific RAS inhibitors, in the plasma and the aorta of those animals by high-performance liquid chromatography (HPLC). Another part of the project is related to the elastase-2 (ELA-2), the AngII producer enzyme in the vascular system. It will be interesting to elucidate the contribution of ELA-2 in the development of the AAA in the mice. This project aims to evaluate the contribution of the RAS components in the abdominal aortic aneurysm pathophysiology induced by Ang II infusion in wild mice (C57/B1-6) and elastase-2 knockout mice (ELA-2 KO). The experimental groups are I) Control C57/BI-6 mice; II) Control knockout ELA-2 mice; III) Induced aneurysm C57/BI-6 mice; IV) Induced aneurysm knockout ELA-2 mice.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

D'AVILA-MESQUITA, CAROLINA; COUTO, ARIEL E. S.; CAMPOS, LIGIA C. B.; VASCONCELOS, TAUANA F.; MICHELON-BARBOSA, JESSYCA; CORSI, CARLOS A. C.; MESTRINER, FABIOLA; PETROSKI-MORAES, BRUNO C.; GARBELLINI-DIAB, MARIA J.; COUTO, DANIEL M. S.; et al. MMP-2 and MMP-9 levels in plasma are altered and associated with mortality in COVID-19 patients. BIOMEDICINE & PHARMACOTHERAPY, v. 142, OCT 2021. (18/23718-8, 19/24369-0, 21/01195-6, 19/21721-4, 20/09999-4, 19/11485-1, 20/03308-0)