Crp3 is a key element for vascular smooth muscle cells mechanotransduction and functional cell phenotype

• Grant number: 23/03079-9
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2023
• End date: September 30, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Ayumi Aurea Miyakawa Yamaguchi
• Grantee: Ayumi Aurea Miyakawa Yamaguchi
• 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 researchers: Carla Cristina Polo ; Christoph Ballestrem ; José Eduardo Krieger ; Miriam Helena Fonseca-Alaniz
• Associated scholarship(s): 25/09911-3 - Crp3 is a key element for vascular smooth muscle cells mechanotransduction and functional cell phenotype, BP.TT; 24/12223-9 - Crp3 modulates aorta biomechanical properties and smooth muscle cells mechanotransduction during aging process., BP.PD; 23/14702-9 - Modulation of Crp3 signalling on focal adhesions and its influence on cell mechanical properties and on extracellular matrix, BP.TT

Abstract

Smooth muscle cells (SMCs) are the major cellular component of the media layer of the vascular wall. They control the contractile properties of the vessel thus modulating the blood flow. It is well demonstrated that vascular mechanical stresses are related to the development of diseases such as atherosclerosis, aneurysm and vein graft disease. Our group has demonstrated that cysteine and glycine-rich protein-3 (Crp3) is expressed in arterial SMCs and usually undetected in venous SMCs. When vein is submitted to arterial hemodynamic condition, mimicking the saphenous vein graft remodeling in the cardiac revascularization, we demonstrated that stretch induces Crp3 expression is venous SMCs. Unpublished data demonstrates that Crp3 is at the focal adhesion and modulates the signaling mediated by Fak. Focal adhesions are connected to the actin cytoskeleton that controls the mechanical properties and contraction response of SMCs, modifying the extracellular matrix (ECM) organization and the mechanical properties of the vascular wall. This process is not completely understood and here we will test the hypothesis that Crp3 modulates SMCs contractile response, cellular and matrix mechanical properties by focal adhesion signaling. It will be used SMCs extracted from rat aorta of wild type and knockout for Crp3 (Crp3-KO). The global molecular expression will be evaluated and the neighboring proteins potential interacting with Crp3 will be evaluated by BioID. That biochemical/molecular information will be associated with cell rigidity and adhesion force evaluated by atomic force microscopy (AFM) and cell contractility assessed by collagen gel contraction assay. Collagen fibers organization will be evaluated by coherent X-ray diffraction image (CDI) and correlated with SMC phenotype and focal adhesion signaling. The understanding of SMC mechanical properties is critical to elucidate vascular pathologies associated to mechanical overload and leverage new therapeutic strategies. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE OLIVEIRA, LUCIANA RENATA; FERNANDES, MATHEUS GIMENEZ; PATANE, JOSE SALVATORE LEISTER; SCHWARTZ, JEAN-MARC; KRIEGER, JOSE EDUARDO; BALLESTREM, CHRISTOPH; MIYAKAWA, AYUMI AUREA. Exploring focal adhesion data: dynamic parameter extraction from FRAP and FLAP experiments using chemical master equation. FRONTIERS IN MOLECULAR BIOSCIENCES, v. 12, p. 15-pg., 2025-05-06. (23/03079-9, 14/50889-7)