Biochemical and molecular analysis of the renin-angiotensin system (RAS) components in the pathophysiology of abdominal aortic aneurysm (AAA) in patients undergoing AAA correction surgery at HCRP-USP

• Grant number: 19/21721-4
• Support type: Scholarships in Brazil - Master
• Effective date (Start): October 01, 2019
• Effective date (End): December 31, 2021
• Field of knowledge: Biological Sciences - Pharmacology
• Principal researcher: Christiane Becari
• Grantee: Jéssyca Michelon Barbosa
• Home 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

An aortic aneurysm is a progressive disease leading to vascular wall deterioration and, gradual aneurysm expansion and, eventually, rupture. The most common aortic aneurysm type is the one that affects its abdominal segment. The incidence and mortality of abdominal aortic aneurysm (AAA) are high, with 1,5 million people in the USA being carriers of this medical condition. The treatment for AAA is the open conventional repair (OR) or the endovascular aneurysm repair (EVAR). There is none known effective AAA medical treatment that can inhibit its growth, development or the rupture risk in human beings. Partly, it is due to a lack of more detailed knowledge about the genetic, cellular and humoral mechanisms in the AAA pathophysiology. The renin-angiotensin system (RAS) participates in several physiological processes in both cardiovascular and renal systems. It also has a significant role in cardiovascular diseases pathophysiology. Experimental data show that continuous angiotensin II (AngII) infusion can induce AAA development in mice. There is also experimental and clinical evidence that the use of RAS inhibitors (angiotensin-converting enzyme inhibitors- ACE inhibitors) and AT1 receptor (AT1R) antagonists can affect the aneurysm stability and reduce the rupture risk. Recently, new RAS modulation paradigms have emerged in which there might be two main RAS pathways: one ACE/Ang II/AT1R deleterious path and, a beneficial ACE-2/Ang 1-7/MASR. Therefore, the present project aims to evaluate the biochemical and molecular analyses. We will use aorta samples and plasma from patients with AAA on surgery's treatment on HCRP-USP and, patients cadaver donors. The biochemical analysis will be done by: 1) to quantify the Ang II, Ang 1-7, Ang IV generation in aorta and plasma by ELISA; 2) to analyze the enzymes that contribute to Ang II, Ang 1- 7 and Ang IV formation and degradation from Ang I in plasma and aortic homogenate obtained from control patients and AAA, using substrates and specific inhibitors of RAS; 3) to investigate mRNA and protein expression of RAS components in the aorta of patients with AAA and control samples. (AU)

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)