ArticleJCI insight2019
Contractile and hemodynamic forces coordinate Notch1b-mediated outflow tract valve formation.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 50 citations in OpenAlex.
- Cardiac mechanotransduction from development to disease.APL bioengineering · 2026Review
- A Continuum of Atrial Peristalsis Initiates the Bicuspid to Quadricuspid Valve Transition.bioRxiv : the preprint server for biology · 2026Article
- Photoaged microplastics disrupt endothelial stretch-sensitive ion channels to impair calcium signaling and vascular integrity.bioRxiv : the preprint server for biology · 2026Article
- Aged Zebrafish as a Spontaneous Model of Cardiac Valvular Disease.Aging cell · 2025Article
- Mechanically activated snai1b coordinates the initiation of myocardial delamination for trabeculation.Nature communications · 2025Article
- A fluid-structure interaction model of the zebrafish aortic valve.Journal of biomechanics · 2025Article
- Intercellular contractile force attenuates chemosensitivity through Notch-MVP-mediated nuclear drug export.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Zebrafish arterial valve development occurs through direct differentiation of second heart field progenitors.Cardiovascular research · 2025Article
- The Interaction Between theInternational journal of molecular sciences · 2025Article
- Advanced Imaging Techniques for Atherosclerosis and Cardiovascular Calcification in Animal Models.Journal of cardiovascular development and disease · 2024Review
- Hemodynamics During Development and Postnatal Life.Advances in experimental medicine and biology · 2024Review
- Integrating 4-D light-sheet fluorescence microscopy and genetic zebrafish system to investigate ambient pollutants-mediated toxicity.The Science of the total environment · 2023Review
- Recent advances in quantifying the mechanobiology of cardiac development via computational modeling.Current opinion in biomedical engineering · 2023Article
- Effect of Blood Flow on Cardiac Morphogenesis and Formation of Congenital Heart Defects.Journal of cardiovascular development and disease · 2022Review
- JAG1-NOTCH4 mechanosensing drives atherosclerosis.Science advances · 2022Article
- Can't handle the stress? Mechanobiology and disease.Trends in molecular medicine · 2022Review
- Following the Beat: Imaging the Valveless Pumping Function in the Early Embryonic Heart.Journal of cardiovascular development and disease · 2022Review
- Computational simulations of the 4D micro-circulatory network in zebrafish tail amputation and regeneration.Journal of the Royal Society, Interface · 2022Article
- Vascular Injury in the Zebrafish Tail Modulates Blood Flow and Peak Wall Shear Stress to Restore Embryonic Circular Network.Frontiers in cardiovascular medicine · 2022Article
- Haemodynamic dependence of mechano-genetic evolution of the cardiovascular system in Japanese medaka.Journal of the Royal Society, Interface · 2021Article
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
Biomechanical forces and endothelial-to-mesenchymal transition (EndoMT) are known to mediate valvulogenesis. However, the relative contributions of myocardial contractile and hemodynamic shear forces remain poorly understood. We integrated 4-D light-sheet imaging of transgenic zebrafish models with moving-domain computational fluid dynamics to determine effects of changes in contractile forces and fluid wall shear stress (WSS) on ventriculobulbar (VB) valve development. Augmentation of myocardial contractility with isoproterenol increased both WSS and Notch1b activity in the developing outflow tract (OFT) and resulted in VB valve hyperplasia. Increasing WSS in the OFT, achieved by increasing blood viscosity through EPO mRNA injection, also resulted in VB valve hyperplasia. Conversely, decreasing myocardial contractility by Tnnt2a morpholino oligonucleotide (MO) administration, 2,3-butanedione monoxime treatment, or Plcγ1 inhibition completely blocked VB valve formation, which could not be rescued by increasing WSS or activating Notch. Decreasing WSS in the OFT, achieved by slowing heart rate with metoprolol or reducing viscosity with Gata1a MO, did not affect VB valve formation. Immunofluorescent staining with the mesenchymal marker, DM-GRASP, revealed that biomechanical force-mediated Notch1b activity is implicated in EndoMT to modulate valve morphology. Altogether, increases in WSS result in Notch1b- EndoMT-mediated VB valve hyperplasia, whereas decreases in contractility result in reduced Notch1b activity, absence of EndoMT, and VB valve underdevelopment. Thus, we provide developmental mechanotransduction mechanisms underlying Notch1b-mediated EndoMT in the OFT.
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