Spatial and temporal variations in hemodynamic forces initiate cardiac trabeculation

Autor: Rongsong Li, Juhyun Lee, Junjie Chen, Cheng-Ming Chuong, Tzung K. Hsiai, René R. Sevag Packard, Hanul Kang, Linda L. Demer, Jeffrey J. Hsu, Kyung In Baek, Adam J. Small, Vijay Vedula, Peng Fei, Yichen Ding, Chih-Chiang Chang, Alison L. Marsden
Rok vydání: 2018
Předmět:
0301 basic medicine
Contraction (grammar)
Organogenesis
Messenger
Pulsatile flow
Hemodynamics
Cardiovascular
Animals
Genetically Modified
0302 clinical medicine
Receptors
Myocytes
Cardiac
GATA1 Transcription Factor
Receptor
Notch1
Zebrafish
biology
Receptors
Notch
Chemistry
General Medicine
Heart Disease
Technical Advance
cardiovascular system
Cardiac
Algorithms
Signal Transduction
Receptor
Notch
Heart Ventricles
Shear force
Cardiology
Embryonic Development
Genetically Modified
Heart failure
Molecular Dynamics Simulation
Development
Stress
03 medical and health sciences
Shear stress
medicine
Animals
RNA
Messenger
Endocardium
Cell Proliferation
erbB-2
Heart Failure
Myocytes
Notch1
Genes
erbB-2
Zebrafish Proteins
medicine.disease
biology.organism_classification
Mechanical
030104 developmental biology
Gene Expression Regulation
Genes
Biophysics
RNA
Stress
Mechanical
030217 neurology & neurosurgery
Zdroj: JCI insight, vol 3, iss 13
Popis: Hemodynamic shear force has been implicated as modulating Notch signaling-mediated cardiac trabeculation. Whether the spatiotemporal variations in wall shear stress (WSS) coordinate the initiation of trabeculation to influence ventricular contractile function remains unknown. Using light-sheet fluorescent microscopy, we reconstructed the 4D moving domain and applied computational fluid dynamics to quantify 4D WSS along the trabecular ridges and in the groves. In WT zebrafish, pulsatile shear stress developed along the trabecular ridges, with prominent endocardial Notch activity at 3 days after fertilization (dpf), and oscillatory shear stress developed in the trabecular grooves, with epicardial Notch activity at 4 dpf. Genetic manipulations were performed to reduce hematopoiesis and inhibit atrial contraction to lower WSS in synchrony with attenuation of oscillatory shear index (OSI) during ventricular development. γ-Secretase inhibitor of Notch intracellular domain (NICD) abrogated endocardial and epicardial Notch activity. Rescue with NICD mRNA restored Notch activity sequentially from the endocardium to trabecular grooves, which was corroborated by observed Notch-mediated cardiomyocyte proliferations on WT zebrafish trabeculae. We also demonstrated in vitro that a high OSI value correlated with upregulated endothelial Notch-related mRNA expression. In silico computation of energy dissipation further supports the role of trabeculation to preserve ventricular structure and contractile function. Thus, spatiotemporal variations in WSS coordinate trabecular organization for ventricular contractile function.
Databáze: OpenAIRE
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