Effect of angiotensin II in redox-dependent mechanoresponse in vascular smooth muscle cells

• Grant number: 19/18450-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2019
• End date: May 31, 2021
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Leonardo Yuji Tanaka
• Grantee: Carolina Morales Portas
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 18/07230-5 - Subcellular mechanisms underlying the convergence between redox and mechanic homeostasis on vascular regulation, AP.JP

Abstract

Cardiovascular diseases are the leading cause of death wordwilde being target of intense investigations. In this sense, studies involving mechanobiologycal processes are needed to clarify such patophysiolgycal mechanisms. Discovery of novel and promissing targets to prevent and treat cardiovascular diseases are of fundamental importance. In the present project we will address the hypothesis that the peptide involved on blood pressure regulation Angiotensin II (Angio II), affects redox dependent processes on mechanoregulation, such as through NADPH oxidase activation and reactive oxygen species generation in vascular smooth muscle cells (VSMC). Overall, literature points that Angio II affects mechanisms beyond blood pressure control. However, there are some potential targets of such regulation which are still unknown such as the local production and its effects on actin cytoskeleton and myosin light chain activation, being necessary to be better addressed. In addition, it is important to investigate if such effects are mediated by ROS production, which would sustain subcellular mechanisms of cardiovascular diseases. Here, we will investigate in VSMC exposed to mechanical stretch such interaction with local Angio II signaling and its NADPH oxidase dependent effect on potential downstream targets including ERK1/2 phosphorylation and on cytoskeleton regulation and mechanism involved on VSMC contraction.