INSERM, U1116, Vandœuvre-lès-Nancy, France; Université de Lorraine, Nancy, France; IBiTech-bioMMeda, Department of Electronics and Information Systems, Ghent University, Gent, Belgium; Department of Pharmacology, European Georges Pompidou Hospital, Assistance Publique Hôpitaux de Paris, France; PARCC INSERM, UMR 970, Paris, France; and University Paris Descartes, Paris, France.
Physiol Rev. 2017 Oct 1;97(4):1555-1617. doi: 10.1152/physrev.00003.2017.
The cushioning function of large arteries encompasses distension during systole and recoil during diastole which transforms pulsatile flow into a steady flow in the microcirculation. Arterial stiffness, the inverse of distensibility, has been implicated in various etiologies of chronic common and monogenic cardiovascular diseases and is a major cause of morbidity and mortality globally. The first components that contribute to arterial stiffening are extracellular matrix (ECM) proteins that support the mechanical load, while the second important components are vascular smooth muscle cells (VSMCs), which not only regulate actomyosin interactions for contraction but mediate also mechanotransduction in cell-ECM homeostasis. Eventually, VSMC plasticity and signaling in both conductance and resistance arteries are highly relevant to the physiology of normal and early vascular aging. This review summarizes current concepts of central pressure and tensile pulsatile circumferential stress as key mechanical determinants of arterial wall remodeling, cell-ECM interactions depending mainly on the architecture of cytoskeletal proteins and focal adhesion, the large/small arteries cross-talk that gives rise to target organ damage, and inflammatory pathways leading to calcification or atherosclerosis. We further speculate on the contribution of cellular stiffness along the arterial tree to vascular wall stiffness. In addition, this review provides the latest advances in the identification of gene variants affecting arterial stiffening. Now that important hemodynamic and molecular mechanisms of arterial stiffness have been elucidated, and the complex interplay between ECM, cells, and sensors identified, further research should study their potential to halt or to reverse the development of arterial stiffness.
大动脉的缓冲功能包括收缩期的扩张和舒张期的回缩，这将脉动流转化为微循环中的稳定流。动脉僵硬度是可扩张性的倒数，与各种慢性常见和单基因心血管疾病的病因有关，是全球发病率和死亡率的主要原因。导致动脉僵硬的第一个组成部分是细胞外基质 (ECM) 蛋白，它支持机械负荷，而第二个重要组成部分是血管平滑肌细胞 (VSMC)，它不仅调节肌球蛋白相互作用以进行收缩，还介导细胞-ECM 平衡中的机械转导。最终，在传导和阻力动脉中，VSMC 的可塑性和信号传导对于正常和早期血管老化的生理学非常重要。
这篇综述总结了目前关于中心压力和拉伸脉动周向应力作为动脉壁重塑的关键机械决定因素的概念，主要取决于细胞骨架蛋白和黏着斑的架构的细胞-ECM 相互作用，导致靶器官损伤的大动脉和小动脉的串扰，以及导致钙化或动脉粥样硬化的炎症途径。我们进一步推测了沿动脉树的细胞硬度对血管壁硬度的贡献。
此外，该综述还提供了最新的关于影响动脉僵硬的基因变异的识别进展。既然已经阐明了动脉僵硬的重要血流动力学和分子机制，并确定了 ECM、细胞和传感器之间的复杂相互作用，那么进一步的研究应该研究它们阻止或逆转动脉僵硬发展的潜力。
