"Young at heart": Regenerative potential linked to immature cardiac phenotypes. (March 2016)

• Record Type: Journal Article
• Authors: Gomes, Renata S.M.; Skroblin, Philipp; Munster, Alex B.; Tomlins, Hannah; Langley, Sarah R.; Zampetaki, Anna; Yin, Xiaoke; Wardle, Fiona C.; Mayr, Manuel
• Is Part Of: Journal of molecular and cellular cardiology. Volume 92(2016:Mar.)
• Page Start: 105
• Page End: 108
• Publication Date: 2016-03
• Subjects: DIGE difference in-gel electrophoresis -- MI myocardial infarction -- LC-MS/MS liquid chromatography tandem mass spectrometry; Regeneration -- Stem cell -- Myofilament -- Cardiomyocyte -- Proteomics; Cardiology -- Periodicals; Heart Diseases -- Periodicals; Molecular Biology -- Periodicals; Cardiologie -- Périodiques; Cardiology; Electronic journals; Periodicals; 616.12
• DOI: 10.1016/j.yjmcc.2016.01.026
• Languages: English
• ISSNs: 0022-2828

Abstract

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 (> 8 weeks old) and adult zebrafish (18 months 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 4 days 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. Graphical abstract: Highlights: Proteomics reveals minimal overlap between adult mouse and adult zebrafish hearts. Gene expression analysis confirms profound differences in myofilament composition. The adult zebrafish heart is more similar to a newborn mouse heart. The relative immaturity is further supported by cardiac microRNA data.