Mechanotransduction and endothelial cell homeostasis: the wisdom of the cell
Mechanotransduction and endothelial cell homeostasis: the wisdom of the cell
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DOI：
10.1152/ajpheart.01047.2006
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发表时间：
2007-03-01
影响因子：
4.8
通讯作者：
Chien, Shu
中科院分区：
文献类型：
--
作者：
Chien, Shu
血管内皮细胞（vascular endothelial cells，ECs）在调节循环功能中起重要作用。机械刺激，包括由循环压力和流量引起的拉伸和剪切应力，通过激活机械传感器、信号通路以及基因和蛋白质表达来调节EC功能。具有明确方向的机械力（例如，脉动剪切应力和存在于动脉树的直线部分中的单轴周向拉伸）仅引起促炎和增殖途径的瞬时分子信号传导，当这种定向机械力持续时，促炎和增殖途径变得下调。相比之下，没有明确方向的机械力（例如，在分支点和复杂几何形状的其它区域看到的扰动流动和相对无方向的拉伸）引起促炎和增殖途径的持续分子信号传导。EC对定向机械刺激的反应涉及EC结构的重塑，以最大限度地减少细胞内应力/应变的改变，并在持续刺激下引起EC信号传导的适应性变化;这些细胞事件构成了维持血管稳态的反馈控制机制，并具有动脉粥样硬化保护作用。这样的反馈机制在复杂几何形状的区域中不能有效地操作，其中机械刺激没有明确的方向，因此将这些区域置于动脉粥样硬化形成的风险中。在主动脉的直的部分中的机械传导诱导的EC适应性过程代表了“细胞的智慧”的情况，作为由Cannon颁布的“身体的智慧”的更一般概念的一部分，以在面对外部扰动时维持细胞内稳态。
Vascular endothelial cells (ECs) play significant roles in regulating circulatory functions. Mechanical stimuli, including the stretch and shear stress resulting from circulatory pressure and flow, modulate EC functions by activating mechanosensors, signaling pathways, and gene and protein expressions. Mechanical forces with a clear direction (e.g., the pulsatile shear stress and the uniaxial circumferential stretch existing in the straight part of the arterial tree) cause only transient molecular signaling of pro-inflammatory and proliferative pathways, which become downregulated when such directed mechanical forces are sustained. In contrast, mechanical forces without a definitive direction (e.g., disturbed flow and relatively undirected stretch seen at branch points and other regions of complex geometry) cause sustained molecular signaling of pro-inflammatory and proliferative pathways. The EC responses to directed mechanical stimuli involve the remodeling of EC structure to minimize alterations in intracellular stress/strain and elicit adaptive changes in EC signaling in the face of sustained stimuli; these cellular events constitute a feedback control mechanism to maintain vascular homeostasis and are atheroprotective. Such a feedback mechanism does not operate effectively in regions of complex geometry, where the mechanical stimuli do not have clear directions, thus placing these areas at risk for atherogenesis. The mechanotransduction-induced EC adaptive processes in the straight part of the aorta represent a case of the "Wisdom of the Cell," as a part of the more general concept of the "Wisdom of the Body" promulgated by Cannon, to maintain cellular homeostasis in the face of external perturbations.