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 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. The relative immaturity of the adult zebrafish heart was further supported by cardiac microRNA data. Our 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.
Highlights
The zebrafish heart has been extensively studied in order to understand its cardioregenerative mechanisms with the hope of translating these findings to humans
The cardiac proteome from adult mice and adult zebrafish was notably different
We observed remarkable differences in the myofilament composition that question the applicability of findings in zebrafish to mammalian hearts
Summary
The zebrafish heart has been extensively studied in order to understand its cardioregenerative mechanisms with the hope of translating these findings to humans. The adult zebrafish heart is able to regenerate within 130 days after having 20–30% of its ventricle damaged by cryoinjury [1]. Genetic ablation of myocytes produces a loss of around 60%, the full extent of which is replaced within 30 days. The large discrepancy in regeneration time is explained by the fact that cryo-injury results in the formation of a large fibrotic area, whereas with genetic ablation no collagen deposition occurs (only a small fibrin clot is observed) [2]. After myocardial infarction (MI) in humans, the formation of scar tissue is an irreversible event. Neonatal mice are capable of myocardial regeneration: upon ventricular apex amputation, 1-day-old mice
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