Department of Chemical and Biological Engineering, The Biofrontiers Institute, University of Colorado, Boulder, CO 80303, USA.
Circ Res. 2013 Jul 5;113(2):186-97. doi: 10.1161/CIRCRESAHA.112.300154.
This review highlights aspects of calcific aortic valve disease that encompass the entire range of aortic valve disease progression from initial cellular changes to aortic valve sclerosis and stenosis, which can be initiated by changes in blood flow (hemodynamics) and pressure across the aortic valve. Appropriate hemodynamics is important for normal valve function and maintenance, but pathological blood velocities and pressure can have profound consequences at the macroscopic to microscopic scales. At the macroscopic scale, hemodynamic forces impart shear stresses on the surface of the valve leaflets and cause deformation of the leaflet tissue. As discussed in this review, these macroscale forces are transduced to the microscale, where they influence the functions of the valvular endothelial cells that line the leaflet surface and the valvular interstitial cells that populate the valve extracellular matrix. For example, pathological changes in blood flow-induced shear stress can cause dysfunction, impairing their homeostatic functions, and pathological stretching of valve tissue caused by elevated transvalvular pressure can activate valvular interstitial cells and latent paracrine signaling cytokines (eg, transforming growth factor-β1) to promote maladaptive tissue remodeling. Collectively, these coordinated and complex interactions adversely impact bulk valve tissue properties, feeding back to further deteriorate valve function and propagate valve cell pathological responses. Here, we review the role of hemodynamic forces in calcific aortic valve disease initiation and progression, with focus on cellular responses and how they feed back to exacerbate aortic valve dysfunction.
这篇综述重点介绍了钙化性主动脉瓣疾病的各个方面，涵盖了主动脉瓣疾病从最初的细胞变化到主动脉瓣狭窄和硬化的整个进展过程，这些变化可能是由主动脉瓣跨瓣血流（血流动力学）和压力的变化引起的。适当的血流动力学对于正常的瓣膜功能和维持很重要，但是病理性的血流速度和压力在宏观到微观尺度上都可能产生深远的后果。在宏观尺度上，血流动力学力对瓣叶表面施加剪切应力，并导致瓣叶组织变形。正如本文综述中所讨论的，这些宏观力被传递到微观尺度，在微观尺度上，它们影响覆盖瓣叶表面的瓣膜内皮细胞和填充瓣膜细胞外基质的瓣膜间质细胞的功能。例如，血流诱导的剪切应力引起的病理性变化会导致功能障碍，损害其稳态功能，而跨瓣压升高引起的瓣膜组织病理性拉伸会激活瓣膜间质细胞和潜在的旁分泌信号细胞因子（例如转化生长因子-β1），促进适应性组织重塑。总的来说，这些协调和复杂的相互作用对大块瓣膜组织特性产生不利影响，反馈作用进一步恶化瓣膜功能，并传播瓣膜细胞的病理性反应。在这里，我们综述了血流动力学在钙化性主动脉瓣疾病发生和进展中的作用，重点介绍了细胞反应以及它们如何反馈加剧主动脉瓣功能障碍。
