Spatial and temporal variations in hemodynamic forces initiate cardiac trabeculation

• DOI: 10.1172/jci.insight.96672
• Publication Date: 2018-07-11T15:01:22Z
• Authors: Juhyun Lee; Vijay Vedula; Kyung In Baek; Junjie Chen; Jeffrey J. Hsu; Yichen Ding; Chih-Chiang Chang; Hanul Kang; Adam Small; Peng Fei; Cheng-ming Chuong; Rongsong Li; Linda Demer; René R. Sevag Pac...; Alison L. Marsden; Tzung K. Hsiai
• Keywords: Endocardium; Contractility; Isovolumetric contraction

Hemodynamic shear force has been implicated as modulating Notch signaling-mediated cardiac trabeculation. Whether the spatiotemporal variations in wall stress (WSS) coordinate initiation of trabeculation to influence ventricular contractile function remains unknown. Using light-sheet fluorescent microscopy, we reconstructed 4D moving domain and applied computational fluid dynamics quantify WSS along trabecular ridges groves. In WT zebrafish, pulsatile developed ridges, with prominent endocardial activity at 3 days after fertilization (dpf), oscillatory grooves, epicardial 4 dpf. Genetic manipulations were performed reduce hematopoiesis inhibit atrial contraction lower synchrony attenuation index (OSI) during development. γ-Secretase inhibitor intracellular (NICD) abrogated activity. Rescue NICD mRNA restored sequentially from endocardium which was corroborated by observed Notch-mediated cardiomyocyte proliferations on zebrafish trabeculae. We also demonstrated vitro that a high OSI value correlated upregulated endothelial Notch-related expression. silico computation energy dissipation further supports role preserve structure function. Thus, organization for