PUBLICATION

"Young at heart": Regenerative potential linked to immature cardiac phenotypes

Authors
Gomes, R.S., Skroblin, P., Munster, A.B., Tomlins, H., Langley, S.R., Zampetaki, A., Yin, X., Wardle, F., Mayr, M.
ID
ZDB-PUB-160202-12
Date
2016
Source
Journal of Molecular and Cellular Cardiology   92: 105-8 (Journal)
Registered Authors
Wardle, Fiona
Keywords
Regeneration, cardiomyocyte, myofilament, stem cell, zebrafish
MeSH Terms
  • Animals
  • Gene Expression Regulation, Developmental
  • Heart/growth & development*
  • Heart Ventricles/growth & development
  • Heart Ventricles/metabolism
  • Humans
  • Mice
  • MicroRNAs/biosynthesis
  • Microfilament Proteins/biosynthesis
  • Muscle Proteins/biosynthesis
  • Myocytes, Cardiac/metabolism
  • Proteome/biosynthesis*
  • Proteome/genetics
  • Proteomics*
  • Regeneration/genetics*
  • Transcriptome
  • Troponin I/biosynthesis
  • Zebrafish/genetics*
  • Zebrafish/growth & development
PubMed
26827899 Full text @ J. Mol. Cell. Cardiol.
Abstract
The adult human myocardium is incapable of regeneration; yet, the zebrafish (Danio rerio) can regenerate damaged myocardium. Similar to the zebrafish heart, hearts of neonatal, but not adult mice are capable of myocardial regeneration. We performed a proteomics analysis of adult zebrafish hearts and compared their protein expression profile to hearts from neonatal and adult mice. Using two-dimensional difference in-gel electrophoresis (DIGE), there was little overlap between the proteome from adult mouse (8weeks old) and adult zebrafish (18months old) hearts. Similarly, there was a significant degree of mismatch between the protein expression in neonatal and adult mouse hearts. Enrichment analysis of the selected proteins revealed over-expression of DNA synthesis-related proteins in the cardiac proteome of the adult zebrafish heart similar to neonatal and 4days old mice, whereas in hearts of adult mice there was a mitochondria-related predominance in protein expression. Importantly, we noted pronounced differences in the myofilament composition: the adult zebrafish heart lacks many of the myofilament proteins of differentiated adult cardiomyocytes such as the ventricular isoforms of myosin light chains and nebulette. Instead, troponin I and myozenin 1 were expressed as skeletal isoforms rather than cardiac isoforms. Our proteomics assessment of zebrafish and mammalian hearts challenges the assertions on the translational potential of cardiac regeneration in the zebrafish model. The immature myofilament composition of the fish heart may explain why adult mouse and human cardiomyocytes lack this endogenous repair mechanism.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping