Section of Pulmonary and Critical Care, Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA.
Antioxid Redox Signal. 2009 Jul;11(7):1651-67. doi: 10.1089/ars.2008.2390.
Blood vessels respond to changes in mechanical load from circulating blood in the form of shear stress and mechanical strain as the result of heart propulsions by changes in intracellular signaling leading to changes in vascular tone, production of vasoactive molecules, and changes in vascular permeability, gene regulation, and vascular remodeling. In addition to hemodynamic forces, microvasculature in the lung is also exposed to stretch resulting from respiratory cycles during autonomous breathing or mechanical ventilation. Among various cell signaling pathways induced by mechanical forces and reported to date, a role of reactive oxygen species (ROS) produced by vascular cells receives increasing attention. ROS play an essential role in signal transduction and physiologic regulation of vascular function. However, in the settings of chronic hypertension, inflammation, or acute injury, ROS may trigger signaling events that further exacerbate smooth muscle hypercontractility and vascular remodeling associated with hypertension and endothelial barrier dysfunction associated with acute lung injury and pulmonary edema. These conditions are also characterized by altered patterns of mechanical stimulation experienced by vasculature. This review will discuss signaling pathways regulated by ROS and mechanical stretch in the pulmonary and systemic vasculature and will summarize functional interactions between cyclic stretch- and ROS-induced signaling in mechanochemical regulation of vascular structure and function.
血管会对循环血液施加的机械负荷（以切应力和机械应变的形式）做出反应，这是心脏搏动导致的结果，其会引起细胞内信号转导的变化，进而导致血管张力、血管活性分子生成和血管通透性、基因调控和血管重构的改变。除血流动力外，在自主呼吸或机械通气过程中的呼吸周期也会导致肺部的微血管受到拉伸。在迄今为止报道的各种机械力诱导的细胞信号通路中，血管细胞产生的活性氧（ROS）的作用受到越来越多的关注。ROS 在血管功能的信号转导和生理调节中发挥着重要作用。然而，在慢性高血压、炎症或急性损伤的情况下，ROS 可能引发信号事件，进一步加剧与高血压相关的平滑肌过度收缩和血管重构，以及与急性肺损伤和肺水肿相关的内皮屏障功能障碍。这些情况的特点还包括血管经历的机械刺激模式发生改变。本综述将讨论 ROS 和机械拉伸在肺血管和全身血管中的调节信号通路，并总结周期性拉伸和 ROS 诱导的信号在血管结构和功能的机械化学调节中的功能相互作用。
