Cardiac hypertrophy involves both myocyte hypertrophy and hyperplasia in anemic zebrafish

Xiaojing Sun, Tiffany Hoage, Ping Bai, Yonghe Ding, Zhenyue Chen, Ruilin Zhang, Wei Huang, Ashad Jahangir, Barry Paw, Yi Gang Li, Xiaolei Xu

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Abstract

Background: An adult zebrafish heart possesses a high capacity of regeneration. However, it has been unclear whether and how myocyte hyperplasia contributes to cardiac remodeling in response to biomechanical stress and whether myocyte hypertrophy exists in the zebrafish. To address these questions, we characterized the zebrafish mutant tr265/tr265, whose Band 3 mutation disrupts erythrocyte formation and results in anemia. Although Band 3 does not express and function in the heart, the chronic anemia imposes a sequential biomechanical stress towards the heart. Methodology/Principal Findings: Hearts of the tr265/tr265 Danio rerio mutant become larger than those of the sibling by week 4 post fertilization and gradually exhibit characteristics of human cardiomyopathy, such as muscular disarray, reactivated fetal gene expression, and severe arrhythmia. At the cellular level, we found both increased individual cardiomyocyte size and increased myocyte proliferation can be detected in week 4 to week 12 tr265/tr265 fish. Interestingly, all tr265/tr265 fish that survive after week-12 have many more cardiomyocytes of smaller size than those in the sibling, suggesting that myocyte hyperplasia allows the long-term survival of these fish. We also show the cardiac hypertrophy process can be recapitulated in wild-type fish using the anemia-inducing drug phenylhydrazine (PHZ). Conclusions/Significance: The anemia-induced cardiac hypertrophy models reported here are the first adult zebrafish cardiac hypertrophy models characterized. Unlike mammalian models, both cardiomyocyte hypertrophy and hyperplasia contribute to the cardiac remodeling process in these models, thus allowing the effects of cardiomyocyte hyperplasia on cardiac remodeling to be studied. However, since anemia can induce effects on the heart other than biomechanical, nonanemic zebrafish cardiac hypertrophy models shall be generated and characterized.

Original languageEnglish (US)
Article numbere6596
JournalPloS one
Volume4
Issue number8
DOIs
StatePublished - Aug 12 2009

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Sun, X., Hoage, T., Bai, P., Ding, Y., Chen, Z., Zhang, R., Huang, W., Jahangir, A., Paw, B., Li, Y. G., & Xu, X. (2009). Cardiac hypertrophy involves both myocyte hypertrophy and hyperplasia in anemic zebrafish. PloS one, 4(8), [e6596]. https://doi.org/10.1371/journal.pone.0006596