Wang Yongtao, Chatterjee Emeli, Li Guoping, Xu Jiahong, Xiao Junjie
Cardiac Regeneration and Ageing Lab, Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong 226011, China; Institute of Cardiovascular Sciences, Shanghai Engineering Research Center of Organ Repair, Joint International Research Laboratory of Biomaterials and Biotechnology in Organ Repair (Ministry of Education), School of Life Science, Shanghai University, Shanghai 200444, China.
Cardiovascular Division of the Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
EBioMedicine. 2024 Dec;110:105412. doi: 10.1016/j.ebiom.2024.105412. Epub 2024 Oct 30.
Force-sensing biophysical cues in microenvironment, including extracellular matrix performances, stretch-mediated mechanics, shear stress and flow-induced hemodynamics, have a significant influence in regulating vascular morphogenesis and cardiac remodeling by mechanotransduction. Once cells perceive these extracellular mechanical stimuli, Piezo activation promotes calcium influx by forming integrin-adhesion-coupling receptors. This induces robust contractility of cytoskeleton structures to further transmit biomechanical alternations into nuclei by regulating Hippo-Yes associated protein (YAP) signaling pathway between cytoplasmic and nuclear translocation. Although biomechanical stimuli are widely studied in cardiovascular diseases, the expression of force-sensing proteins in response to cardiovascular mechanotransduction has not been systematically concluded. Therefore, this review will summarize the force-sensing Piezo, cytoskeleton and YAP proteins to mediate extracellular mechanics, and also give the prominent emphasis on intrinsic connection of these mechanical proteins and cardiovascular mechanotransduction. Extensive insights into cardiovascular mechanics may provide some new strategies for cardiovascular clinical therapy.
微环境中的力敏感生物物理线索，包括细胞外基质特性、拉伸介导的力学、剪切应力和流动诱导的血流动力学，通过机械转导对调节血管形态发生和心脏重塑具有重大影响。一旦细胞感知到这些细胞外机械刺激，Piezo激活通过形成整合素-黏附-偶联受体促进钙内流。这会诱导细胞骨架结构产生强大的收缩力，通过调节细胞质和细胞核转位之间的Hippo-Yes相关蛋白（YAP）信号通路，进一步将生物力学变化传递到细胞核。尽管生物力学刺激在心血管疾病中得到了广泛研究，但力敏感蛋白在心血管机械转导中的表达尚未得到系统总结。因此，本综述将总结力敏感的Piezo、细胞骨架和YAP蛋白介导细胞外力学的情况，并着重强调这些机械蛋白与心血管机械转导的内在联系。对心血管力学的深入了解可能为心血管临床治疗提供一些新策略。
