title: Cardiac hypertrophy involves both myocyte hypertrophy and hyperplasia in anemic zebrafish.
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.
  
  
  RESULTS
  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
  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.
authors: Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
authors: Xiaojing
authors: X
authors: Sun
authors: Tiffany
authors: T
authors: Hoage
authors: Ping
authors: P
authors: Bai
authors: Yonghe
authors: Y
authors: Ding
authors: Zhenyue
authors: Z
authors: Chen
authors: Ruilin
authors: R
authors: Zhang
authors: Wei
authors: W
authors: Huang
authors: Ashad
authors: A
authors: Jahangir
authors: Barry
authors: B
authors: Paw
authors: Yi-Gang
authors: YG
authors: Li
authors: Xiaolei
authors: X
authors: Xu
mesh_terms: D000740:Anemia / Q000150:complications*; D000818:Animals; D015153:Blotting, Western; D006332:Cardiomegaly / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D020287:In Situ Nick-End Labeling; D008854:Microscopy, Electron; D009206:Myocardium / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015027:Zebrafish