Effects of mechanical forces on signal transduction and gene expression in endothelial cells
Effects of mechanical forces on signal transduction and gene expression in endothelial cells
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DOI：
10.1161/01.hyp.31.1.162
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发表时间：
1998-01-01
期刊：
影响因子：
8.3
通讯作者：
Shyy, JYJ
中科院分区：
文献类型：
--
作者：
Chien, S;Li, S;Shyy, JYJ
流体剪切力和周向拉伸在维持血管内稳态方面起着重要作用，也可能是动脉粥样硬化和高血压等心血管疾病的病理生理因素。利用流道和拉伸装置作为体外模型，有助于阐明血管内皮细胞对切应力或机械应变的信号转导和基因表达的机制。切应力是血流和血管测量的函数，机械应变是跨壁压力以及血管的机械性能和几何形状的函数。研究发现，剪切力可以增强多种蛋白激酶的活性，从而调节内皮细胞中许多信号蛋白的磷酸化，如粘着斑处的蛋白和丝裂原激活的蛋白激酶通路中的蛋白。在这些信号级联的下游，多种转录因子如AP-1、NF-kappa B、Sp-1和Egr-1被激活。这些转录因子作用于相应的顺式元件，在内皮细胞中诱导编码血管激活剂、黏附分子、单核细胞趋化因子和生长因子的基因，从而调节血管结构和功能。机械应变对内皮细胞的一些影响与剪应力相似，如信号通路和激活的基因，但有差异，如反应的时间进程。研究机械力对信号转导和基因表达的影响，有助于深入了解血液动力学因素调节血管生理和病理生理学的分子机制。
Fluid shear stress and circumferential stretch play important roles in maintaining the homeostasis of the blood vessel, and they can also be pathophysiological factors in cardiovascular diseases such as atherosclerosis and hypertension. The uses of flow channels and stretch devices as in vitro models have helped to elucidate the mechanisms of signal transduction and gene expression in cultured endothelial cells in response to shear stress, which is a function of blood flow and vascular metry, or mechanical strain, which is a function of transmural pressure and the mechanical properties and geometry of the vessel. Shear stress has been found to increase the activities of a number of kinases to modulate the phosphorylation of many signaling proteins in endothelial cells, eg, the proteins in focal adhesion sites and the proteins in the mitogen-activated protein kinase pathways. Downstream to such signaling cascades, multiple transcription factors such as AP-1, NF-kappa B, Sp-1, and Egr-1 are activated. The actions of these transcription factors on the corresponding cis-elements result in the induction of genes encoding for vasoactivators, adhesion molecules, monocyte chemoattractants, and growth factors in endothelial cells, thus modulating vascular structure and function. Some of the effects of mechanical strain on endothelial cells are similar to those by shear stress, eg, the signaling pathways and the genes activated, but there are differences, eg, the time course of the responses. Studies on the effects of mechanical forces on signal transduction and gene expression provide insights into the molecular mechanisms by which hemodynamic factors regulate vascular physiology and pathophysiology.