Study of nitric oxide-dependent modulation of physiologic and pathologic cyclic stretch set point in endothelial cells

• Grant number: 19/18448-4
• 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: Geovana Stefani Garcia
• 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

The deep scientific knowledge concerning the mechanisms involved in cardiovascular diseases is important for their prevention and treatment. In this sense, mechanotransduction-based regulation is such a remarkable regulator, as modulated by hemodynamic forces such as cyclic stretch, which triggers adaptive responses resulting in vascular protection or diseases. Nitric oxide (NO) levels must be considered due to its important regulation on endothelial cell integrity, being considered a major determinant on endothelial patency. The lack of regulation on cyclic stretch caused by disturbed blood flow forces is crucial for vascular tonus alterations and for inflammation, mediated by endothelial wall damage. Although it is not clear there are some evidences pointing redox processes regulating NO bioavailability through antioxidant response and acute NO production by iNOS. Thus, the aim of this project is to investigate the role of NO on physiological and pathological stretch on endothelial cells. In order to address that, endothelial cells will be submitted to distinct stretch levels and the expression of several genes involved with protection or endothelial inflammation will be measured. In addition, fingerprints of NO or its ROS derived products will be assayed in order to evaluate if NO can be a modulator of the stretch set point in endothelial cells.