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The regenerative capacity of zebrafish reverses cardiac failure caused by genetic cardiomyocyte depletion.

Publication ,  Journal Article
Wang, J; Panáková, D; Kikuchi, K; Holdway, JE; Gemberling, M; Burris, JS; Singh, SP; Dickson, AL; Lin, Y-F; Sabeh, MK; Werdich, AA; Yelon, D ...
Published in: Development
August 2011

Natural models of heart regeneration in lower vertebrates such as zebrafish are based on invasive surgeries causing mechanical injuries that are limited in size. Here, we created a genetic cell ablation model in zebrafish that facilitates inducible destruction of a high percentage of cardiomyocytes. Cell-specific depletion of over 60% of the ventricular myocardium triggered signs of cardiac failure that were not observed after partial ventricular resection, including reduced animal exercise tolerance and sudden death in the setting of stressors. Massive myocardial loss activated robust cellular and molecular responses by endocardial, immune, epicardial and vascular cells. Destroyed cardiomyocytes fully regenerated within several days, restoring cardiac anatomy, physiology and performance. Regenerated muscle originated from spared cardiomyocytes that acquired ultrastructural and electrophysiological characteristics of de-differentiation and underwent vigorous proliferation. Our study indicates that genetic depletion of cardiomyocytes, even at levels so extreme as to elicit signs of cardiac failure, can be reversed by natural regenerative capacity in lower vertebrates such as zebrafish.

Duke Scholars

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Published In

Development

DOI

EISSN

1477-9129

Publication Date

August 2011

Volume

138

Issue

16

Start / End Page

3421 / 3430

Location

England

Related Subject Headings

  • Zebrafish
  • Regeneration
  • Myocytes, Cardiac
  • Heart Failure
  • Heart
  • Cell Death
  • Animals
  • 42 Health sciences
  • 32 Biomedical and clinical sciences
  • 31 Biological sciences
 

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Wang, J., Panáková, D., Kikuchi, K., Holdway, J. E., Gemberling, M., Burris, J. S., … Poss, K. D. (2011). The regenerative capacity of zebrafish reverses cardiac failure caused by genetic cardiomyocyte depletion. Development, 138(16), 3421–3430. https://doi.org/10.1242/dev.068601
Wang, Jinhu, Daniela Panáková, Kazu Kikuchi, Jennifer E. Holdway, Matthew Gemberling, James S. Burris, Sumeet Pal Singh, et al. “The regenerative capacity of zebrafish reverses cardiac failure caused by genetic cardiomyocyte depletion.Development 138, no. 16 (August 2011): 3421–30. https://doi.org/10.1242/dev.068601.
Wang J, Panáková D, Kikuchi K, Holdway JE, Gemberling M, Burris JS, et al. The regenerative capacity of zebrafish reverses cardiac failure caused by genetic cardiomyocyte depletion. Development. 2011 Aug;138(16):3421–30.
Wang, Jinhu, et al. “The regenerative capacity of zebrafish reverses cardiac failure caused by genetic cardiomyocyte depletion.Development, vol. 138, no. 16, Aug. 2011, pp. 3421–30. Pubmed, doi:10.1242/dev.068601.
Wang J, Panáková D, Kikuchi K, Holdway JE, Gemberling M, Burris JS, Singh SP, Dickson AL, Lin Y-F, Sabeh MK, Werdich AA, Yelon D, Macrae CA, Poss KD. The regenerative capacity of zebrafish reverses cardiac failure caused by genetic cardiomyocyte depletion. Development. 2011 Aug;138(16):3421–3430.
Journal cover image

Published In

Development

DOI

EISSN

1477-9129

Publication Date

August 2011

Volume

138

Issue

16

Start / End Page

3421 / 3430

Location

England

Related Subject Headings

  • Zebrafish
  • Regeneration
  • Myocytes, Cardiac
  • Heart Failure
  • Heart
  • Cell Death
  • Animals
  • 42 Health sciences
  • 32 Biomedical and clinical sciences
  • 31 Biological sciences