Shear-induced endothelial mechanotransduction: the interplay between reactive oxygen species (ROS) and nitric oxide (NO) and the pathophysiological implications.
Shear-induced endothelial mechanotransduction: the interplay between reactive oxygen species (ROS) and nitric oxide (NO) and the pathophysiological implications.
复制标题
DOI：
10.1186/1423-0127-21-3
复制
发表时间：
2014-01-13
影响因子：
11
通讯作者：
Wang DL
中科院分区：
文献类型：
--
作者：
Hsieh HJ;Liu CA;Huang B;Tseng AH;Wang DL
血流动力学剪切应力，即血流产生的作用在血管内皮细胞上的摩擦力，是正常生理条件下内皮细胞维持稳态所必需的。内皮细胞上的机械传感器检测剪切应力并将其转化为生化信号以触发血管适应性反应。在各种剪切诱导的信号分子中，活性氧（ROS）和一氧化氮（NO）与血管稳态和疾病有关。在这篇综述中，我们探讨了由剪切诱导的信号（机械转导）引起的分子、细胞和血管过程，重点是ROS和NO的作用，并讨论了可能导致血管过度重塑从而驱动动脉粥样硬化病理过程的机制。目前的证据表明，NADPH氧化酶是血流状态下内皮细胞生成ROS的主要细胞来源之一。血流模式和剪切的大小决定了内皮细胞产生ROS的数量，通常不规则的血流模式（紊乱或振荡）比规则的血流模式（稳定或脉动）产生更高水平的ROS。ROS的产生与NO的产生密切相关，ROS水平升高导致NO的生物利用度降低，这在暴露于不规则血流的内皮细胞中经常观察到。一氧化氮生物利用度低的部分原因是活性氧与一氧化氮反应形成过氧亚硝酸盐，这是一种可能引发许多促动脉粥样硬化事件的关键分子。在不同的血流模式和条件下，ROS和RNS（活性氮物种）的差异产生调节了内皮基因的表达，从而导致了不同的血管反应。此外，ROS/RNS能够促进调节蛋白（包括s -谷胱甘肽基化、s -亚硝基化和酪氨酸硝化）的特异性翻译后修饰，这些修饰构成了与心血管病理生理相关的化学信号。总的来说，局部血流动力学环境与由此产生的调节蛋白的氧化和s -亚硝化修饰之间的动态相互作用对于随后的血管稳态是重要的。根据现有证据，研究人员提出，正常的血流模式会产生较低水平的ROS和较高的NO生物利用度，从而创造一个抗动脉粥样硬化的环境。另一方面，不规则的血流模式导致更高水平的ROS和更低的NO生物利用度，从而引发促动脉粥样硬化作用。
Hemodynamic shear stress, the blood flow-generated frictional force acting on the vascular endothelial cells, is essential for endothelial homeostasis under normal physiological conditions. Mechanosensors on endothelial cells detect shear stress and transduce it into biochemical signals to trigger vascular adaptive responses. Among the various shear-induced signaling molecules, reactive oxygen species (ROS) and nitric oxide (NO) have been implicated in vascular homeostasis and diseases. In this review, we explore the molecular, cellular, and vascular processes arising from shear-induced signaling (mechanotransduction) with emphasis on the roles of ROS and NO, and also discuss the mechanisms that may lead to excessive vascular remodeling and thus drive pathobiologic processes responsible for atherosclerosis. Current evidence suggests that NADPH oxidase is one of main cellular sources of ROS generation in endothelial cells under flow condition. Flow patterns and magnitude of shear determine the amount of ROS produced by endothelial cells, usually an irregular flow pattern (disturbed or oscillatory) producing higher levels of ROS than a regular flow pattern (steady or pulsatile). ROS production is closely linked to NO generation and elevated levels of ROS lead to low NO bioavailability, as is often observed in endothelial cells exposed to irregular flow. The low NO bioavailability is partly caused by the reaction of ROS with NO to form peroxynitrite, a key molecule which may initiate many pro-atherogenic events. This differential production of ROS and RNS (reactive nitrogen species) under various flow patterns and conditions modulates endothelial gene expression and thus results in differential vascular responses. Moreover, ROS/RNS are able to promote specific post-translational modifications in regulatory proteins (including S-glutathionylation, S-nitrosylation and tyrosine nitration), which constitute chemical signals that are relevant in cardiovascular pathophysiology. Overall, the dynamic interplay between local hemodynamic milieu and the resulting oxidative and S-nitrosative modification of regulatory proteins is important for ensuing vascular homeostasis. Based on available evidence, it is proposed that a regular flow pattern produces lower levels of ROS and higher NO bioavailability, creating an anti-atherogenic environment. On the other hand, an irregular flow pattern results in higher levels of ROS and yet lower NO bioavailability, thus triggering pro-atherogenic effects.
登录
查看更多内容
影响因子：
4.8
作者：
Chen, XL;Varner, SE;Kunsch, C
通讯作者：
Kunsch, C
影响因子：
4.4
作者：
Chen, Yi-Ju;Ku, Wei-Chi;Chen, Yu-Ju
通讯作者：
Chen, Yu-Ju
DOI：
10.1152/ajpheart.2001.281.1.h22
发表时间：
2001-07-01
影响因子：
4.8
作者：
Bao, XP;Lu, CY;Frangos, JA
通讯作者：
Frangos, JA
影响因子：
20.3
作者：
Dekker, RJ;van Soest, S;Horrevoets, AJG
通讯作者：
Horrevoets, AJG
DOI：
10.1152/ajpheart.00242.2010
发表时间：
2010-09-01
影响因子：
4.8
作者：
Dikalova, Anna E.;Gongora, Maria Carolina;Griendling, Kathy K.
通讯作者：
Griendling, Kathy K.