Cho Jae Min, Poon Mong Lung Steve, Zhu Enbo, Wang Jing, Butcher Jonathan T, Hsiai Tzung
Division of Cardiology, Department of Medicine, David Geffen School of Medicine, UCLA.
Department of Medicine, Greater Los Angeles VA Healthcare System.
Curr Opin Biomed Eng. 2023 Jun;26. doi: 10.1016/j.cobme.2022.100438. Epub 2022 Dec 21.
Abnormal cardiac development is intimately associated with congenital heart disease. During development, a sponge-like network of muscle fibers in the endocardium, known as trabeculation, becomes compacted. Biomechanical forces regulate myocardial differentiation and proliferation to form trabeculation, while the molecular mechanism is still enigmatic. Biomechanical forces, including intracardiac hemodynamic flow and myocardial contractile force, activate a host of molecular signaling pathways to mediate cardiac morphogenesis. While mechanotransduction pathways to initiate ventricular trabeculation is well studied, deciphering the relative importance of hemodynamic shear vs. mechanical contractile forces to modulate the transition from trabeculation to compaction requires advanced imaging tools and genetically tractable animal models. For these reasons, the advent of 4-D multi-scale light-sheet imaging and complementary multiplex live imaging via micro-CT in the beating zebrafish heart and live chick embryos respectively. Thus, this review highlights the complementary animal models and advanced imaging needed to elucidate the mechanotransduction underlying cardiac ventricular development.
心脏发育异常与先天性心脏病密切相关。在发育过程中，心内膜中海绵状的肌纤维网络（称为小梁化）会变得致密。生物力学力调节心肌分化和增殖以形成小梁化，但其分子机制仍然不明。生物力学力，包括心内血流动力学和心肌收缩力，激活一系列分子信号通路来介导心脏形态发生。虽然启动心室小梁化的机械转导途径已得到充分研究，但要解读血流动力学剪切力与机械收缩力在调节从小梁化到致密化转变中的相对重要性，需要先进的成像工具和易于进行基因操作的动物模型。基于这些原因，分别在跳动的斑马鱼心脏和活鸡胚胎中出现了四维多尺度光片成像以及通过微型CT进行的互补多重活体成像。因此，本综述强调了阐明心室发育背后机械转导所需的互补动物模型和先进成像技术。
