Endothelial to mesenchymal transition during vein arterialization remodeling: the role of mechanical stretch on endothelial plasticity

• Grant number: 14/06844-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: September 01, 2014
• End date: August 31, 2018
• Field of knowledge: Health Sciences - Medicine
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Ayumi Aurea Miyakawa Yamaguchi
• Grantee: Thais Girão 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: 13/17368-0 - Cardiovascular genomics: mechanisms & novel therapeutics - CVGen mech2ther, AP.TEM

Abstract

Saphenous vein graft is widely used for cardiac revascularization in ischemic myocardium. However, adaptive response to the new hemodynamic condition predisposes the vein graft to occlusion due to the remodeling with increased extracellular matrix and cells expressing ±-SMA. Experimental evidence demonstrates that endothelial to mesenchymal transition (EndMT) is one source of ±-SMA positive cells during vascular remodeling. EndMT is characterized by endothelial markers reduction, gain of mesenchymal markers and increased deposition of matrix. This process is dependent on TGF² signaling and recently it was demonstrated that combined stimulation of IL1b + TGFb2 enhances this phenotypic transition in vitro. Vein grafts are submitted to changes in hemodynamic forces, such as increased shear stress and cyclic strain. It is demonstrated that endothelial cells subjected to laminar shear stress are resistant to EndMT induction and there is lack of information regarding to stretch influence in this process. The hypothesis of the present work is that mechanical stretch induces and/or enhances the EndMT process in a pro-inflammatory (IL1b) and pro-fibrotic environment (TGFb). Data from our laboratory shows that IL1b is increased during vein graft arterialization remodeling and we want to associate with mechanical stimulus to understand the contribution of EndMT to the pathological vascular remodeling. (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)

MIYAKAWA, AYUMI A.; GIRAO-SILVA, THAIS; KRIEGER, JOSE E.; EDELMAN, ELAZER R.. Rapamycin activates TGF receptor independently of its ligand: implications for endothelial dysfunction. Clinical Science, v. 132, n. 4, p. 437-447, FEB 28 2018. (13/17368-0, 14/06844-9)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SILVA, Thais Girão da. Molecular mechanisms involved in endothelial phenotype in response to physical and chemical stimuli. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.