The role of Nrf2 and redox signaling in aldosterone-induced vascular dysfunction

• Grant number: 19/22303-1
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: February 01, 2020
• End date: May 31, 2020
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Rita de Cassia Aleixo Tostes Passaglia
• Grantee: Daniel Rodrigues
• Supervisor: Rhian Merry Touyz
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University of Glasgow, Scotland
• Associated to the scholarship: 18/05298-1 - Contribution of the transcription factor Nrf2 for the vascular alterations associated with arterial hypertension induced by aldosterone, BP.IC

Abstract

Chronic increases in aldosterone (Aldo) levels (hyperaldosteronism) is deleterious for the cardiovascular system. It increases blood pressure and induces hypertension. In the cardiovascular system, Aldo stimulates generation of reactive oxygen species (ROS),which contribute to vascular dysfunction, by increasing vascular smooth muscle tone and by stimulating development and progression of cardiac and vascular remodeling, among other effects.Redox signaling is important in many cellular processes, including signal transduction, gene expression, cell cycle and metabolism. Both the structure and function of many key proteins involved in various cellular functions are modified in cells under oxidative stress, even changing how cells respond to redox alterations. Nuclear factor erythroid 2-related factor 2 (Nrf2), it's one of the main factors in the adaptive response to oxidative stress. Nrf2 activity is impaired in many diseases including arterial hypertension, diabetes and atherosclerosis.Considering that (i) Nrf2 is a redox-regulated system, (ii) post-translational modifications of proteins, including reversible and irreversible oxidation, may interfere with Nrf2 activation and effects and (iii) Aldo induces vascular ROS generation and vascular dysfunction, this study proposes to determine whether aldosterone, by stimulating ROS generation and oxidative stress, impairs Nrf2 transcriptional factor signaling and activity in vascular cells. (AU)