Plasmatic and tissue assessment of inflammatory mediators, angiotensin I and II receptors, renin, angiotensin-converting enzymes, chymase and elastase-2 in patients with and without abdominal aortic aneurysm submitted to surgery at HCRP-USP

• Grant number: 23/08275-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: July 01, 2023
• End date: November 30, 2024
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Christiane Becari
• Grantee: Vinicius Flora Dugaich
• 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

Abdominal aortic aneurysm (AAA) is a degenerative inflammatory disease that poses a serious risk of rupture if not treated promptly. The renin-angiotensin system (RAS) is a cascade of enzymatic reactions that can currently be divided into two axes. One axis consists of angiotensin-converting enzyme (ACE), chymase, elastase-2, angiotensin (Ang) I and II, and AT1 receptor (AT1R). The other axis involves angiotensin-converting enzyme 2 (ACE2), angiotensin 1-7, AT2 receptor (AT2R), and MAS receptor (MASR). It is believed that the ACE/Ang II/AT1R axis is deleterious, while the ACE2/Ang 1-7/MASR axis is beneficial, with both axes having counter-regulatory effects in physiological and pathological conditions.Experimental and clinical studies indicate that the use of RAS inhibitors (ACE inhibitors and AT1 receptor antagonists) may have an effect on stabilizing and reducing the risk of AAA rupture. However, so far, no effective pharmacological treatment for AAA has been identified that can inhibit its growth, progression, or rupture risk in humans. This is partly due to a lack of deeper understanding of the genetic, cellular, and humoral mechanisms involved in AAA pathophysiology. Therefore, it is crucial to understand the role of the RAS in the pathophysiology of aneurysmal disease. Thus, this study investigated the presence of the ACE/Ang II/AT1R and ACE2/Ang 1-7/MASR axes of the RAS in aortas obtained from AAA patients and controls.Therefore, the objective of this study is to quantify and evaluate the components of the RAS in the pathophysiology of AAA. Protein expression analysis was performed using Western blotting, and plasma and tissue analysis of AAA patients and controls were conducted using ELISA. mRNA expression was evaluated using qPCR, and patient demographic and clinical data were analyzed.The results so far demonstrate that the majority of control and AAA patients were males (81.2% AAA vs. 63.1% Control). Smokers or ex-smokers accounted for 93.7% in the AAA group and 36.8% in the control group. Regarding the expression of RAS components, an imbalance is observed, with the inflammatory axis components (ACE/ELA2/AngII/AT1r) being more expressed, contrasting with the decreased expression of the protective axis components (ACE2/Ang1-7/AT2r/MASr) in abdominal aortic aneurysm. Another important difference noted, as observed by ELISA, is the differential expression of RAS components in tissue and blood, indicating the distinct roles of this cascade of reactions in the human body. (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)

MESTRINER, FABIOLA; FRANCISCO, DANIELY F.; CAMPOS, LIGIA C. B.; COUTO, ARIEL E. S.; FRAGA-SILVA, THAIS F. C.; DUGAICH, VINICIUS FLORA; AVILA-MESQUITA, CAROLINA D.; KOVACS, HENRIQUE ZUKOWSKI; VASCONCELOS, JOCIANY L.; MILANI, ELIZABETE R.; et al. Alpha 1-acid glycoprotein is upregulated in severe COVID-19 patients and decreases neutrophil NETs in SARS-CoV-2 infection. CYTOKINE, v. 176, p. 12-pg., 2024-01-31. (19/21721-4, 23/14949-4, 20/03308-0, 18/23718-8, 18/26553-0, 23/08275-0, 20/05691-5, 19/24369-0, 19/11485-1, 22/13048-0, 21/08796-5, 20/09999-4)