Molecular Biology Division, Department of Biochemistry, Carl Peter von Dietrich Laboratory, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
PLoS One. 2020 Nov 19;15(11):e0241040. doi: 10.1371/journal.pone.0241040. eCollection 2020.
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.
内皮细胞(ECs)会受到血流产生的切应力(SS)等物理力的作用,这会导致其形态、生理和基因表达发生显著变化。心血管系统中异常的机械力会影响血栓形成、高血压和动脉粥样硬化等疾病的发展。本研究调查了暴露于正常和改变的 SS 下的 ECs 中糖胺聚糖(GAGs)、蛋白聚糖和细胞外基质分子的表达。将 ECs 暴露于 12 dyn/cm2(动脉生理条件)和 4 dyn/cm2(动脉病理条件)的 SS 下。随后,对 ECs 进行免疫荧光、qPCR、GAG 生物合成分析和基于细胞的测定。SS 诱导 ECs 形态发生变化。改变的 SS 还会产生其他病理后果,包括抑制黏附、刺激迁移和毛细血管样管形成,以及 GAG 合成增加。我们观察到 syndecan-4、perlecan、decorin、纤连蛋白和胶原 III α1 以及生长因子(包括 VEGF-A 和 TGFβ-1)的表达增加。暴露于 SS 的 ECs 表现出细胞外基质重塑以及细胞-基质和细胞-细胞相互作用分子的表达。本研究有助于了解血管生物学如何受到机械力的影响,以及这些分子如何在心血管疾病中受到影响。