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Title: Effects of extended pharmacological disruption of zebrafish embryonic heart biomechanical environment on cardiac function, morphology, and gene expression
Authors: Foo, Yoke Yin 
Motakis, Efthymios 
Tiang, Zenia
Shen, Shuhao 
Lai, Jason Kuan Han 
Chan, Wei Xuan 
Wiputra, Hadi 
Chen, Nanguang 
Chen, Ching Kit 
Winkler, Christoph 
Foo, Roger Sik Yin 
Yap, Choon Hwai 
Keywords: BDM stoppage of embryonic heart
biofluid dynamics
computational fluid dynamics
embryonic heart biomechanics
embryonic heart mechanobiology
Issue Date: 4-Jun-2021
Publisher: John Wiley and Sons Inc
Citation: Foo, Yoke Yin, Motakis, Efthymios, Tiang, Zenia, Shen, Shuhao, Lai, Jason Kuan Han, Chan, Wei Xuan, Wiputra, Hadi, Chen, Nanguang, Chen, Ching Kit, Winkler, Christoph, Foo, Roger Sik Yin, Yap, Choon Hwai (2021-06-04). Effects of extended pharmacological disruption of zebrafish embryonic heart biomechanical environment on cardiac function, morphology, and gene expression. Developmental Dynamics 250 (12) : 1759-1777. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: Background: Biomechanical stimuli are known to be important to cardiac development, but the mechanisms are not fully understood. Here, we pharmacologically disrupted the biomechanical environment of wild-type zebrafish embryonic hearts for an extended duration and investigated the consequent effects on cardiac function, morphological development, and gene expression. Results: Myocardial contractility was significantly diminished or abolished in zebrafish embryonic hearts treated for 72 hours from 2 dpf with 2,3-butanedione monoxime (BDM). Image-based flow simulations showed that flow wall shear stresses were abolished or significantly reduced with high oscillatory shear indices. At 5 dpf, after removal of BDM, treated embryonic hearts were maldeveloped, having disrupted cardiac looping, smaller ventricles, and poor cardiac function (lower ejected flow, bulboventricular regurgitation, lower contractility, and slower heart rate). RNA sequencing of cardiomyocytes of treated hearts revealed 922 significantly up-regulated genes and 1,698 significantly down-regulated genes. RNA analysis and subsequent qPCR and histology validation suggested that biomechanical disruption led to an up-regulation of inflammatory and apoptotic genes and down-regulation of ECM remodeling and ECM–receptor interaction genes. Biomechanics disruption also prevented the formation of ventricular trabeculation along with notch1 and erbb4a down-regulation. Conclusions: Extended disruption of biomechanical stimuli caused maldevelopment, and potential genes responsible for this are identified. © 2021 The Authors. Developmental Dynamics published by Wiley Periodicals LLC on behalf of American Association for Anatomy.
Source Title: Developmental Dynamics
ISSN: 1058-8388
DOI: 10.1002/dvdy.378
Rights: Attribution 4.0 International
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