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THE ROLE OF NRF2 AND REDOX SIGNALING IN ALDOSTERONE-INDUCED VASCULAR DYSFUNCTION

Grant number: 19/22303-1
Support type:Scholarships abroad - Research Internship - Scientific Initiation
Effective date (Start): February 01, 2020
Effective date (End): May 31, 2020
Field of knowledge:Biological Sciences - Pharmacology - Cardiorenal Pharmacology
Principal Investigator:Rita de Cassia Aleixo Tostes Passaglia
Grantee:Daniel Rodrigues
Supervisor abroad: Rhian Merry Touyz
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Local de pesquisa : 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 thecardiovascular system. It increases blood pressure and induces hypertension. In the cardiovascularsystem, Aldo stimulates generation of reactive oxygen species (ROS),which contribute to vasculardysfunction, by increasing vascular smooth muscle tone and by stimulating development andprogression of cardiac and vascular remodeling, among other effects.Redox signaling is important in many cellular processes, including signal transduction, geneexpression, cell cycle and metabolism. Both the structure and function of many key proteins involvedin various cellular functions are modified in cells under oxidative stress, even changing how cellsrespond to redox alterations. Nuclear factor erythroid 2-related factor 2 (Nrf2), it's one of the mainfactors in the adaptive response to oxidative stress. Nrf2 activity is impaired in many diseasesincluding arterial hypertension, diabetes and atherosclerosis.Considering that (i) Nrf2 is a redox-regulated system, (ii) post-translational modifications ofproteins, including reversible and irreversible oxidation, may interfere with Nrf2 activation andeffects and (iii) Aldo induces vascular ROS generation and vascular dysfunction, this study proposesto determine whether aldosterone, by stimulating ROS generation and oxidative stress, impairs Nrf2transcriptional factor signaling and activity in vascular cells