Endothelial cell behavior under arterial hypertension in vitro and its impact on osteogenesis

• Grant number: 17/18349-0
• Support type: Scholarships in Brazil - Master
• Effective date (Start): September 01, 2017
• Effective date (End): February 28, 2019
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal researcher: Willian Fernando Zambuzzi
• Grantee: Thaís Silva Pinto
• Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated research grant: 14/22689-3 - Microvesicle/proteins-mediated paracrine signaling among bone and endothelial cells during bone development and regeneration, AP.JP

Abstract

Endothelial cells respond phenotypically to mechanical forces generated by the blood flow, secreting important repertory of trophic factors and which has been related to mechanisms of bone remodeling, as proposed by Kusumbe et al. (2014). In this sense, our proposal is characterized cell morphological changes and the molecular mechanisms required during the cellular response to arterial hypertension, as well as evaluating their effects on osteogenesis in vitro, by using a biological model ongoing in our research group. Hypertension has been considered a major public health problem in Brazil, and its consequences on bone health has been not evaluted fully. For this, HUVEC endothelial cells will be subjected to shear stress, under conditions of hypertension and later this model will be evaluated at a cellular and molecular aspects, including epigenetic. Specifically, we intend to: 1. Perform a proteomic characterization of the released factors from endothelial and smooth muscle cells; 2. Analyze potential signal transduction pathways involved with rearrangement of actin filaments; 3. To estimate an influence of the model on remodeling mechanisms of the extracellular matrix through expression and matrices of matrix metalloproteinases (MMP2 and MMP9); 4. Determination of epigenetic mechanisms by analyzing the levels of 5meC and 5hmeC. Establishing biochemical, cellular and ultrastructural events of endothelial/smooth muscle cells, submitted or not to the Shear-Stress model in hypertensive or non-hypertensive conditions, will be of extreme relevance at the moment to establish the repertoire of proteins synthesized and released impacting surrounding tissues. (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)

PINTO, THAIS SILVA; DA COSTA FERNANDES, CELIO JUNIOR; DA SILVA, RODRIGO AUGUSTO; GOMES, ANDERSON MOREIRA; SOUZA VIEIRA, JOSE CAVALCANTE; PADILHA, PEDRO DE M.; ZAMBUZZI, WILLIAN F. c-Src kinase contributes on endothelial cells mechanotransduction in a heat shock protein 70-dependent turnover manner. Journal of Cellular Physiology, v. 234, n. 7, p. 11287-11303, JUL 2019. Web of Science Citations: 3.