Study of subcellular mechanisms of redox and tension-associated processes in vascular smooth muscle cells (VSMC) in a model of pro-atherogenic blood flow

• Grant number: 19/09829-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: June 01, 2019
• End date: May 31, 2021
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Leonardo Yuji Tanaka
• Grantee: Jaime Matheus da Silva
• 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 among the leading cause of death in the world. Atherosclerosis has great relevance because it's the main inflammatory cardiovascular disease that disturbs the blood flow and, in addition to the risk factors, increases the chances of more severe complications to the patient, leading to death. Although well described, studies on the atherosclerotic process are lacking especially regarding vascular remodeling induced by disturbed blood flow. In this project, we hypothesized that vascular remodeling, after a mechanical disturbance, is controlled by the fine regulation of the production of reactive oxygen species (ROS) in vascular smooth muscle cells (VSMCs) that influence the return to cellular tensile homeostasis. Understanding how this mechanism works, will make clearer how the changes undergone in this process induce a pro-atherogenic profile. We will use partial carotid ligation as a model of atherosclerosis induction; genetic silencing by transfection using cDNA and siRNA; analysis of vessel viscoelastic properties; and analysis of mechanical stimuli in isolated vessels stabilized in a pressurized system. It is hoped to gain a better understanding of the redox patterns involved in the process of returning to tension homeostasis with this project, as well as to obtain an overview of how changes in this subcellular pathway induce a pro-atherogenic profile in the vessels and proliferative profile in the VSMCs. (AU)