The role of the cysteine and glycine-rich protein-3 (CRP3) in mechanosensing of cardiovascular smooth muscle cells

• Grant number: 17/50298-7
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2018
• End date: July 31, 2023
• Field of knowledge: Health Sciences - Medicine
• Agreement: University of Manchester
• Mobility Program: SPRINT - Projetos de pesquisa - Mobilidade
• Principal Investigator: Ayumi Aurea Miyakawa Yamaguchi
• Grantee: Ayumi Aurea Miyakawa Yamaguchi
• Principal researcher abroad: Christoph Ballestrem
• Institution abroad: University of Manchester, England
• 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

Abstract

About 8% of men aged over 65 years show abdominal aortic aneurysms (AAA) and over 80% of patients where and AAA are ruptured die. The AAA formation involves the rupture of extracellular matrix fibers and loss of smooth muscle cells leading to the vascular wall narrowing. The underlying molecular mechanisms of how AAA develops are unknown. During the aneurysm development, there is an increase of mechanical stress in the vascular wall due to the decrease of smooth muscle cells and extracellular matrix (ECM) content. This proposal aims to shed more light into the function of the protein CRP3 (cysteine and glycine-rich protein-3) and how it regulates the cellular response to mechanical strain. Following striking pilot data, we hypothesize that CRP3 mediates its function through components of cell-matrix interaction sites. To examine this hypothesis we will employ state-of-the-art-advanced fluorescence imaging and analyses how CRP3 contributes to molecular dynamics and interactions of the adhesion complex proteins under mechanical stimuli smooth muscle cells experience in vivo. The collaboration will help the team members involved in this project to gain, (I) valuable data that enable to expand the collaboration and submit a follow up grant application of larger scope; (II) to interdisciplinary insight into the methods applied by the partner laboratory; (III) to potentially expend the collaborative efforts to other laboratories situated in the Universities. A lona-term aim will be to help identifying necessary new targets of how to prevent and treat AAA. (AU)