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

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.

Paracrine Shear-Stress-Dependent Signaling from Endothelial Cells Affects Downstream Endothelial Function and Inflammation

“…Similar to our experimental model, Russo and colleagues [72] demonstrated that rabbit aortic endothelial cells exposed for 4 h to sub-physiological and physiological values of shear stress have a different tendency to form tube-like structures. Moreover, they confirmed that mRNA expression of pro-angiogenic factors such as vascular endothelial growth factor A (VEGF-A), transforming growth factor-beta 1 (TGF-β1) and transforming growth factor-beta 3 (TGF-β3) is higher in EC cells exposed to pathological shear stresses compared to physiological shear stress.…”

Endothelial inflammation and neutrophil transmigration are modulated by extracellular matrix composition in an inflammation-on-a-chip model

“…Collagen I is well established as a 2D coating or 3D ECM for endothelial cells, as it robustly supports adherence and monolayer formation 49 , 55 – 58 . In contrast, studies on culturing endothelial cells on basement membrane extracts (BMEs) such as geltrex or matrigel focus on induction of tube formation, modelling angiogenesis 62 – 64 . Our initial findings mirror these approaches, with successful vessel formation on collagen I, and vessel retraction and tube formation against geltrex.…”

Extracellular matrix: paving the way to the newest trends in atherosclerosis

“…HS accounts for 50–90% of the total GAG pool, while the rest is composed of CS and hyaluronan [ 10 ]. In a recent study, endothelial cells exposed to pathological shear stress increased GAG synthesis, secretion and content, compared with those exposed to physiological shear stress [ 11 ▪ ]. The extent of atherosclerosis progression is associated with thinning of vascular endothelial glycocalyx, attributed to diminished expression of HSPGs [ 12 ▪ ].…”