Abstract 278: Developmental Contractile Function Modulates Notch1b-Mediated Valvular Leaflet Development
Arteriosclerosis, Thrombosis, and Vascular Biology
Abstract
Cardiac valve formation is a complex process affected by blood flow, but the mechanotransduction mechanisms underlying valvulogenesis remain incompletely understood. Using four-dimensional (4-D) light-sheet imaging, we evaluated the effects of pharmacological and genetic hemodynamic modulation on ventriculobulbar (VB) valve formation in the outflow tracts (OFT) of transgenic Tg(fli1a:GFP) zebrafish embryos. Treatment with isoproterenol increased heart rate and cardiac contractility, increased Notch1b activity in the OFT, and resulted in the development of hyperplastic VB valve leaflets. While metoprolol treatment reduced heart rate without affecting contractility, there were no significant differences in Notch1b expression in the OFT or valve morphology. Meanwhile, BDM treatment significantly reduced heart rate and contractility, reduced Notch1b expression in the OFT, and prevented the formation of normal VB valve leaflets. Similarly, no VB valve leaflets were seen in the cloche mutant or Tnnt2a MO-injected embryos. Additionally, increasing blood viscosity by micro-injection of embryos with EPO mRNA increased Notch1b activity in the OFT and led to hyperplastic VB valve leaflets, but decreasing blood viscosity by gata1a MO micro-injection did not have any significant effect. Further, activation of the Notch signaling pathway with micro-injection of NICD mRNA resulted in hyperplastic VB valve leaflets. By integrating advanced optics with zebrafish genetics at the interface of developmental cardiac mechanics, we provide mechanotransduction insights into cardiac valve development within the OFT.
Information & Authors
Information
Published In
Copyright
© 2018 by American Heart Association, Inc.
History
Published in print: May 2018
Published online: 12 March 2019
Keywords
Authors
Metrics & Citations
Metrics
Citations
Download Citations
If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.
View Options
View options
PDF and All Supplements
Download PDF and All SupplementsLogin options
Check if you have access through your login credentials or your institution to get full access on this article.
Personal login Institutional LoginPurchase Options
Purchase this article to access the full text.
eLetters(0)
eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.
Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.