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

• Published in: PloS one Vol. 15; no. 11; p. e0241040
• Main Authors: Russo, T A, Banuth, A M M, Nader, H B, Dreyfuss, J L
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19.11.2020; Public Library of Science (PLoS)
• Subjects: Angiogenesis; Animals; Arteries - metabolism; Arteriosclerosis; Atherosclerosis; Binding sites; Biochemistry; Biology and Life Sciences; Biosynthesis; Blood flow; Capillary tubes; Cardiovascular diseases; Cardiovascular system; Cell adhesion & migration; Cell culture; Cells, Cultured; Collagen (type III); Collagen - metabolism; Cytology; Decorin; Development and progression; Endothelial cells; Endothelial Cells - metabolism; Endothelial Cells - pathology; Endothelium; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Epithelial cells; Exposure; Extracellular matrix; Extracellular Matrix - metabolism; Extracellular Matrix - pathology; Extracellular Matrix Proteins - metabolism; Fibronectin; Fibronectins - metabolism; Gene expression; Glycosaminoglycans; Glycosaminoglycans - metabolism; Growth factors; Health aspects; Heparan sulfate; Heparan Sulfate Proteoglycans - metabolism; Hypertension; Immunofluorescence; Laboratories; Mechanical stimuli; Medicine and Health Sciences; Molecular biology; Morphogenesis - physiology; Morphology; Neovascularization; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - pathology; Perlecan; Physical Sciences; Physiological aspects; Physiology; Proteoglycans; Rabbits; Research and Analysis Methods; Risk factors; Shear stress; Stress (Physiology); Stress, Mechanical; Syndecan; Thromboembolism; Thrombosis; Transforming Growth Factor beta1 - metabolism; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; Veins & arteries; Brazil; United States > US; Texas; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0241040

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.