Altered shear stress on endothelial cells leads to remodeling of extracellular matrix and induction of angiogenesis.

T A Russo,A M M Banuth,H B Nader,J L Dreyfuss,Gianfranco Pintus

doi:10.1371/journal.pone.0241040

T A Russo, A M M Banuth + Show 3 more

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https://doi.org/10.1371/journal.pone.0241040

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Journal: PloS one	Publication Date: Nov 19, 2020
Citations: 39	License type: CC BY 4.0

Affiliation: Universidade Federal de São Paulo

Abstract

Endothelial cells (ECs) are subjected to physical forces such as shear stress (SS) induced by blood flow that leads to significant changes in morphology, physiology and gene expression. The abnormal mechanical forces applied in the cardiovascular system can influence the development of conditions and diseases such as thrombosis, hypertension and atherosclerosis. This study investigated the expression of glycosaminoglycans (GAGs), proteoglycans and extracellular matrix molecules in ECs exposed to normal and altered SS. ECs were exposed to SS of 12 dyn/cm2 (artery physiological condition) and 4 dyn/cm2 (artery pathological condition). Subsequently, ECs were subjected to immunofluorescence, qPCR, GAG biosynthesis analyses and cell-based assays. SS induced changes in ECs morphology. There were other pathological consequences of altered SS, including inhibited adhesion, stimulation of migration and capillary-like tube formation, as well as increases of GAG synthesis. We observed higher expression of syndecan-4, perlecan, decorin, fibronectin and collagen III α1 and growth factors, including VEGF-A and TGFβ-1. ECs exposed to SS displayed extracellular matrix remodeling as well as expression of cell-matrix and cell-cell interaction molecules. This study contributes to the understanding of how vascular biology is affected by mechanical forces and how these molecules can be affected in cardiovascular diseases.

Highlights

Vascular endothelial cells (ECs) are exposed to mechanical forces such as stretching, tension, compression and shear stress that modulate their functional properties; this phenomenon is known as mechanotransduction, and it may be physiologic or pathologic [1, 2]
These results demonstrate a slight increase of gene expression of angiogenic growth factors (VEGF-A, TGF-β1 and TGF-β3) in ECs exposed to pathological SS (4 dyn/cm2) compared to physiological SS (12 dyn/cm2), suggesting a possible increase in angiogenesis, corroborating the results of the capillary-like tube formation assay
Sdc4 expression is increased, playing anti-thrombotic and anti-atherogenic roles. Both results regarding heparan sulfate (HS) synthesis and Sdc4 expression are in accordance with results the literature, because we demonstrated that ECs exposed to pathological SS showed increased expression of Sdc4 compared to ECs exposed to physiological SS

Summary

Introduction

Vascular endothelial cells (ECs) are exposed to mechanical forces such as stretching, tension, compression and shear stress that modulate their functional properties; this phenomenon is known as mechanotransduction, and it may be physiologic or pathologic [1, 2]. Mechanotransduction is the conversion of mechanical forces into molecular and cellular responses [3]. This usually results in intracellular changes to compensate for the stress. Blood flow regulates the internal diameter of the arteries in two ways: by constricting and relaxing vascular smooth muscle cells and by reorganizing the vessel wall (ECs and extracellular matrix) [1, 4]. In both cases, the endothelium is the key factor, acting as a mechanical sensor. Cell components such as glycocalyx and extracellular matrix (ECM) interact with the cytoskeleton and are activated by mechanical deformation [5]

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