HEMODYNAMICS AND THE VASCULAR ENDOTHELIUM

HEMODYNAMICS AND THE VASCULAR ENDOTHELIUM
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DOI:
10.1115/1.2895532
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发表时间:
1993-11-01
影响因子:
1.7
通讯作者:
NEREM, RM
NEREM, RM
中科院分区:
工程技术4区
文献类型:
--
作者:
NEREM, RM

文献摘要

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内皮细胞曾经被认为是一种被动的、非血栓形成的屏障,现在被认为是血管生物学和病理生物学中的动态参与者。其动态性质的一部分是由于血管系统的血流动力学所施加的机械环境的影响。在过去的二十年里,关于血流动力学对血管内皮细胞的影响已经有了很多的研究。这在一定程度上是通过体内实验实现的;然而,在过去的15年里,许多实验室转向应用体外细胞培养系统来研究流动和周期性拉伸对血管内皮细胞生物学的影响。综上所述,这些研究表明,流动和相关的剪切力调节内皮细胞的结构和功能。使用循环拉伸的细胞培养研究提供了类似的证据。此外,机械环境的这些影响延伸到基因表达水平,存在着对mRNA的差异调控。一个关键的问题是,内皮细胞如何识别其所处的机械环境,以及在这样做之后,这种环境是如何转化为观察到的结构和功能的变化的?尽管我们对识别事件的了解仍然有限,但关于响应机械刺激的信号转导的研究表明,许多已知由化学激动剂触发的第二信使也参与了机械信号的转导。在过去的20年里,我们对系统血流动力学对血管内皮细胞生物学的影响的重要性的认识有了很大的增长,无论是在调节血管的正常生物学方面,还是作为动脉粥样硬化病变的分布和发展的决定因素方面,我们都有很大的进步,然而,仍然有很多需要学习的地方。
The endothelium, once thought to be a passive, non-thrombogenic barrier, is now recognized as being a dynamic participant in vascular biology and pathobiology. Part of its dynamic nature is due to the influence of the mechanical environment imposed by the hemodynamics of the vascular system. Over the past two decades much has been learned about the influence of hemodynamics on the vascular endothelium. This has been in part through in vivo experiments; however, in the past 15 years a number of laboratories have turned to the application of in vitro cell culture systems to investigate the influence of flow and cyclic stretch on the biology of vascular endothelium. Taken together these studies demonstrate that flow and the associated shear stress modulate both endothelial cell structure and function. Cell culture studies employing cyclic stretch provide similar evidence. Furthermore, these effects of mechanical environment extend to the gene expression level, with there being a differential regulation of mRNA. A critical question is how does an endothelial cell recognize the mechanical environment in which it resides and, having done so, how is this transduced into the changes in structure and function observed? Although our knowledge of the recognition events remains limited, studies on signal transduction in response to a mechanical stimulus indicate that many of the second messengers known to be triggered by chemical agonists also are involved in transducing a mechanical signal. Over the past 20 years our understanding of the importance of the influence of the mechanical environment imposed by the hemodynamics of the system on vascular endothelial biology, both in the regulation of the normal biology of blood vessels and as a determinant of the distribution and development of atherosclerotic lesions, has grown immensely, however, there is still much to be learned.