PUBLICATION
Cardiac hypertrophy involves both myocyte hypertrophy and hyperplasia in anemic zebrafish
- Authors
- Sun, X., Hoage, T., Bai, P., Ding, Y., Chen, Z., Zhang, R., Huang, W., Jahangir, A., Paw, B., Li, Y.G., and Xu, X.
- ID
- ZDB-PUB-090814-13
- Date
- 2009
- Source
- PLoS One 4(8): e6596 (Journal)
- Registered Authors
- Chen, Zhenyue, Hoage, Tiffany R., Huang, Wei, Paw, Barry, Sun, Xiaojing, Xu, Xiaolei, Zhang, Ruilin
- Keywords
- Zebrafish, Heart, Muscle cells, Cardiac ventricles, Cardiac hypertrophy, Red blood cells, Anemia, Fishes
- MeSH Terms
-
- Anemia/complications*
- Animals
- Blotting, Western
- Cardiomegaly/complications
- Cardiomegaly/pathology*
- Cardiomegaly/physiopathology
- In Situ Nick-End Labeling
- Microscopy, Electron
- Myocardium/pathology*
- Reverse Transcriptase Polymerase Chain Reaction
- Zebrafish
- PubMed
- 19672293 Full text @ PLoS One
Citation
Sun, X., Hoage, T., Bai, P., Ding, Y., Chen, Z., Zhang, R., Huang, W., Jahangir, A., Paw, B., Li, Y.G., and Xu, X. (2009) Cardiac hypertrophy involves both myocyte hypertrophy and hyperplasia in anemic zebrafish. PLoS One. 4(8):e6596.
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, re-activated 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, non-anemic zebrafish cardiac hypertrophy models shall be generated and characterized.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping