Cheng Chak Kwong, Wang Nanping, Wang Li, Huang Yu
Department of Biomedical Sciences and Tung Biomedical Sciences Centre, City University of Hong Kong, China (C.K.C., L.W., Y.H.).
Laboratory for Molecular Vascular Biology and Bioengineering, and Wuhu Hospital, Health Science Center, East China Normal University, Shanghai (N.W.).
Circ Res. 2025 Mar 28;136(7):752-772. doi: 10.1161/CIRCRESAHA.124.325685. Epub 2025 Mar 27.
Hemodynamic shear stress, the frictional force exerted by blood flow on the endothelium, mediates vascular homeostasis. This review examines the biophysical nature and biochemical effects of shear stress on endothelial cells, with a particular focus on its impact on cardiovascular pathophysiology. Atherosclerosis develops preferentially at arterial branches and curvatures, where disturbed flow patterns are most prevalent. The review also highlights the range of shear stress across diverse human arteries and its temporal variations, including aging-related alterations. This review presents a summary of the critical mechanosensors and flow-sensitive effectors that respond to shear stress, along with the downstream cellular events that they regulate. The review evaluates experimental models for studying shear stress in vitro and in vivo, as well as their potential limitations. The review discusses strategies targeting shear stress, including pharmacological approaches, physiological means, surgical interventions, and gene therapies. Furthermore, the review addresses emerging perspectives in hemodynamic research, including single-cell sequencing, spatial omics, metabolomics, and multiomics technologies. By integrating the biophysical and biochemical aspects of shear stress, this review offers insights into the complex interplay between hemodynamics and endothelial homeostasis at the preclinical and clinical levels.
血流动力学剪切应力是血流作用于内皮细胞的摩擦力,介导血管稳态。本综述探讨了剪切应力对内皮细胞的生物物理性质和生化效应,特别关注其对心血管病理生理学的影响。动脉粥样硬化优先发生在动脉分支和弯曲处,这些地方紊乱的血流模式最为普遍。该综述还强调了不同人类动脉中剪切应力的范围及其随时间的变化,包括与衰老相关的改变。本综述总结了对剪切应力作出反应的关键机械传感器和血流敏感效应器,以及它们所调节的下游细胞事件。该综述评估了体外和体内研究剪切应力的实验模型及其潜在局限性。该综述讨论了针对剪切应力的策略,包括药理学方法、生理学手段、手术干预和基因治疗。此外,该综述还阐述了血流动力学研究中的新观点,包括单细胞测序、空间组学、代谢组学和多组学技术。通过整合剪切应力的生物物理和生化方面,本综述在临床前和临床水平上深入探讨了血流动力学与内皮稳态之间的复杂相互作用。