Mechanical stretch implications for vascular endothelial cells: Altered extracellular matrix synthesis and remodeling in pathological conditions

Abstract

Aims: Cardiovascular diseases such as hypertension, thrombosis and atherosclerosis are responses to mechanical forces applied to the endothelium. Endothelial cells respond to hemodynamic mechanical forces such as cellular mechanical stretching. We investigated the expression of glycosaminoglycans, proteoglycans and other extracellular matrix molecules in endothelial cells subjected to various mechanical stimuli.

Main methods: Endothelial cells were subjected to mechanical stretch in a vacuum system FlexCell™ to 5% (physiological condition) and 15% (pathological condition), for 4 h or 24 h. Culture plates not subjected to strain were used as controls. Subsequently, ECs were subjected to immunofluorescence, real-time PCR, PCR array, glycosaminoglycans biosynthesis using metabolic radiolabeling with ³⁵S-sulfate and cell behavior assays (adhesion, migration and capillary tube formation).

Key findings: Mechanical stretch induced changes in endothelial cell morphology. Pathological consequences of mechanical stretch included inhibited migration in 2-fold and capillary-like tube formation in 2-fold, when compared to physiological condition after 4 h of ECs exposure; it also reduced total sulfated glycosaminoglycans synthesis thereabout 1.5-fold. Pathological mechanical stretch conditions induced higher expression after 24 h of ECs exposure to mechanical stretch of syndecan-4 (3.5-fold), perlecan (9.1-fold), decorin (5.7-fold), adhesive proteins as fibronectin (5.6-fold) and collagen III α1 (2.2-fold) and growth factors, including VEGF-A (7.3-fold) and TGFβ-1 (14.6-fold) and TGFβ-3 (4.3-fold).

Significance: Exposure of endothelial cells to mechanical stretch influenced remodeling of the extracellular matrix as well as cell-matrix interactions. These studies improve understanding of how vascular biology is affected by mechanical forces and how these molecules behave in cardiovascular diseases.

Keywords: Endothelial cells; Mechanical stretch; Molecular biology; Proteoglycans; Vascular diseases.