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

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)