Role of extracellular matrix components in mechanotransduction of endothelial cells

• Grant number: 14/10156-0
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2014
• End date: February 28, 2017
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Juliana Luporini Dreyfuss Regatieri
• Grantee: Juliana Luporini Dreyfuss Regatieri
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: José Eduardo Mourão Santos ; Marcelo Andrade de Lima

Abstract

The mechanical stresses alter the structural and functional properties of the cells (called mechanotransduction) at cellular and molecular levels. The extracellular matrix (ECM) and cell surface components, such as the glycocalyx , are activated by mechanical forces. The response of endothelial cells (ECs) to mechanotransduction is important for the homeostasis of the circulatory system, and abnormal responses to these forces are involved in cardiovascular diseases. In this research project the expression of ECM molecules in endothelial cells and vascular smooth muscle cells (VSMCs) in culture exposed to different mechanotransduction stimuli as the shear stress and cell stretching will be investigated. Both the shear stress and the cell stretch will be performed under physiological and pathological conditions and after these stimuli the cells will be assessed for the expression of ECM molecules using immunofluorescence, quantitative PCR, glycosaminoglycans analysis, triggered signaling pathways, and proteomic analysis . Furthermore, in vivo experiments will investigate the arteries of apolipoprotein E knockout mice, an atherosclerosis animal model. The in vivo experiments include: image analysis using high frequency ultrasound of the atherosclerotic blood vessels followed by histopathological and immunohistochemical analysis besides the quantitative PCR of ECM molecules. These studies will help to better understand how the vascular biology and ECM molecules are affected by mechanical effects, and how these molecules behave in cardiovascular diseases. (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)

RUSSO, T. A.; BANUTH, A. M. M.; NADER, H. B.; DREYFUSS, J. L.. Altered shear stress on endothelial cells leads to remodeling of extracellular matrix and induction of angiogenesis. PLoS One, v. 15, n. 11, NOV 19 2020. (14/10156-0)

RUSSO, T. A.; STOLL, D.; NADER, H. B.; DREYFUSS, J. L.. Mechanical stretch implications for vascular endothelial cells: Altered extracellular matrix synthesis and remodeling in pathological conditions. Life Sciences, v. 213, p. 214-225, NOV 15 2018. (14/10156-0)