Effects of disturbed flow on vascular endothelium: pathophysiological basis and clinical perspectives.
Effects of disturbed flow on vascular endothelium: pathophysiological basis and clinical perspectives.
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DOI：
10.1152/physrev.00047.2009
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发表时间：
2011-01
影响因子：
33.6
通讯作者：
Chien S
中科院分区：
文献类型：
--
作者：
Chiu JJ;Chien S
血管内皮细胞（EC）暴露于血流动力学力，其调节健康和疾病中的EC功能和血管生物学/病理生物学。在血管系统中，流动模式和血液动力学力是不均匀的。在动脉树的直线部分，血流通常是层流，壁面剪切应力高且定向;在分支和弯曲部分，血流受到低壁面剪切应力的不均匀和不规则分布的干扰。高剪切应力的持续层流上调EC基因和蛋白质的表达，这些基因和蛋白质对动脉粥样硬化具有保护作用，而与往复运动相关的低剪切应力的扰动流通常上调促进动脉粥样硬化形成的EC基因和蛋白质。这些发现导致了这样的概念，即分支点和弯曲处的扰动流动模式导致动脉粥样硬化病变的优先定位。血流紊乱还导致术后新生内膜增生，并导致临床疾病的病理生理学，如支架内再狭窄、静脉旁路移植失败和移植血管病变以及主动脉瓣钙化。在静脉系统中，由回流、流出道阻塞和/或淤滞引起的扰动流动导致静脉炎症和血栓形成，并因此发展成慢性静脉疾病。了解扰动流对内皮细胞的影响，可以提供复杂的流动模式在血管疾病发病机制中的作用的机理见解，并有助于阐明静止（非致动脉粥样硬化/非血栓形成）和活化（致动脉粥样硬化/血栓形成）内皮细胞之间的表型和功能差异。本文综述了目前的知识，在EC的生理和病理生理的作用，以及其临床意义的扰动流。这些信息有助于我们理解血流紊乱的血管龛病变发展的病因，并有助于产生新的治疗干预方法。
Vascular endothelial cells (ECs) are exposed to hemodynamic forces, which modulate EC functions and vascular biology/pathobiology in health and disease. The flow patterns and hemodynamic forces are not uniform in the vascular system. In straight parts of the arterial tree, blood flow is generally laminar and wall shear stress is high and directed; in branches and curvatures, blood flow is disturbed with nonuniform and irregular distribution of low wall shear stress. Sustained laminar flow with high shear stress upregulates expressions of EC genes and proteins that are protective against atherosclerosis, whereas disturbed flow with associated reciprocating, low shear stress generally upregulates the EC genes and proteins that promote atherogenesis. These findings have led to the concept that the disturbed flow pattern in branch points and curvatures causes the preferential localization of atherosclerotic lesions. Disturbed flow also results in postsurgical neointimal hyperplasia and contributes to pathophysiology of clinical conditions such as in-stent restenosis, vein bypass graft failure, and transplant vasculopathy, as well as aortic valve calcification. In the venous system, disturbed flow resulting from reflux, outflow obstruction, and/or stasis leads to venous inflammation and thrombosis, and hence the development of chronic venous diseases. Understanding of the effects of disturbed flow on ECs can provide mechanistic insights into the role of complex flow patterns in pathogenesis of vascular diseases and can help to elucidate the phenotypic and functional differences between quiescent (nonatherogenic/nonthrombogenic) and activated (atherogenic/thrombogenic) ECs. This review summarizes the current knowledge on the role of disturbed flow in EC physiology and pathophysiology, as well as its clinical implications. Such information can contribute to our understanding of the etiology of lesion development in vascular niches with disturbed flow and help to generate new approaches for therapeutic interventions.
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