Endothelial cellular response to altered shear stress

Endothelial cellular response to altered shear stress
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DOI:
10.1152/ajplung.2001.281.3.l529
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发表时间:
2001-09-01
影响因子:
4.9
通讯作者:
Nerem, RM
Nerem, RM
中科院分区:
医学2区
文献类型:
--
作者:
Fisher, AB;Chien, S;Nerem, RM

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内皮细胞通常持续暴露于显著影响其表型的机械力。这次研讨会介绍了有关内皮细胞对与血流相关的切应力的反应的最新信息。已经提出的内皮细胞剪切应力机械传感器包括膜受体激酶、整联蛋白、G蛋白、离子通道、细胞间连接蛋白、膜脂质(例如,与小窝相关的那些)和细胞骨架。这些传感器与信号级联相关,这些信号级联与活性氧、一氧化氮和各种转录因子等反应相互作用或导致其产生。内皮细胞适应持续的剪切力,并且从正常剪切力的增加或减少导致信号传导事件。用于研究内皮细胞反应的体外模型必须考虑剪切应力的模式(例如,稳定流与振荡流),用于细胞生长的支架(例如,基底膜或其它细胞类型如平滑肌细胞),以及流动适应的程度。这些细胞反应对于理解与高血压相关的剪切应力增加或与血栓性闭塞相关的剪切应力降低的病理生理学效应具有重要意义。
Endothelial cells are normally exposed constantly to mechanical forces that significantly influence their phenotype. This symposium presented recent information concerning endothelial cell responses to shear stress associated with blood flow. Endothelial cell shear stress mechanosensors that have been proposed include membrane receptor kinases, integrins, G proteins, ion channels, intercellular junction proteins, membrane lipids (e.g., those associated with caveolae), and the cytoskeleton. These sensors are linked to signaling cascades that interact with or result in generation of reactive oxygen species, nitric oxide, and various transcription factors among other responses. Endothelial cells adapt to sustained shear stress, and either an increase or decrease from normal shear leads to signaling events. In vitro models for the study of endothelial cell responses must consider the pattern of shear stress (e.g., steady vs. oscillatory flow), the scaffold for cell growth (e.g., basement membrane or other cell types such as smooth muscle cells), and the extent of flow adaptation. These cellular responses have major relevance for understanding the pathophysiological effects of increased shear stress associated with hypertension or decreased shear stress associated with thrombotic occlusion.