Wu David, Birukov Konstantin
Section of Pulmonary and Critical Care, Department of Medicine, University of Chicago, Chicago, IL, United States.
Department of Anesthesia, University of Maryland, Baltimore, MD, United States.
Front Bioeng Biotechnol. 2019 Jul 19;7:172. doi: 10.3389/fbioe.2019.00172. eCollection 2019.
Lungs are the most vascular part of humans, accepting the totality of cardiac output in a volume much smaller than the body itself. Due to this cardiac output, the lung microvasculature is subject to mechanical forces including shear stress and cyclic stretch that vary with the cardiac and breathing cycle. Vessels are surrounded by extracellular matrix which dictates the stiffness which endothelial cells also sense and respond to. Shear stress, stiffness, and cyclic stretch are known to influence endothelial cell state. At high shear stress, endothelial cells exhibit cell quiescence marked by low inflammatory markers and high nitric oxide synthesis, whereas at low shear stress, endothelial cells are thought to "activate" into a pro-inflammatory state and have low nitric oxide. Shear stress' profound effect on vascular phenotype is most apparent in the arterial vasculature and in the pathophysiology of vascular inflammation. To conduct the flow of blood from the right heart, the lung microvasculature must be rigid yet compliant. It turns out that excessive substrate rigidity or stiffness is important in the development of pulmonary hypertension and chronic fibrosing lung diseases via excessive cell proliferation or the endothelial-mesenchymal transition. Recently, a new body of literature has evolved that couples mechanical sensing to endothelial phenotypic changes through metabolic signaling in clinically relevant contexts such as pulmonary hypertension, lung injury syndromes, as well as fibrosis, which is the focus of this review. Stretch, like flow, has profound effect on endothelial phenotype; metabolism studies due to stretch are in their infancy.
肺是人体血管最丰富的部位，接受全部心输出量，而其容积远小于人体本身。由于这种心输出量，肺微血管系统会受到包括剪切应力和周期性拉伸在内的机械力作用，这些力会随心脏和呼吸周期而变化。血管被细胞外基质包围，细胞外基质决定了血管的硬度，内皮细胞也能感知并对其做出反应。已知剪切应力、硬度和周期性拉伸会影响内皮细胞状态。在高剪切应力下，内皮细胞表现为细胞静止，其特征是炎症标志物水平低且一氧化氮合成高，而在低剪切应力下，内皮细胞被认为会“激活”为促炎状态且一氧化氮水平低。剪切应力对血管表型的深远影响在动脉血管系统和血管炎症的病理生理学中最为明显。为了使血液从右心流出，肺微血管系统必须既坚硬又有弹性。事实证明，在肺动脉高压和慢性纤维化性肺病的发展过程中，过高的底物硬度或刚性通过过度的细胞增殖或内皮-间充质转化起着重要作用。最近，出现了一批新的文献，在肺动脉高压、肺损伤综合征以及纤维化等临床相关背景下，通过代谢信号将机械传感与内皮细胞表型变化联系起来，这也是本综述的重点。与血流一样，拉伸对内皮细胞表型也有深远影响；关于拉伸引起的代谢研究尚处于起步阶段。
