title: "Young at heart": Regenerative potential linked to immature cardiac phenotypes.
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.
authors.affiliation: King's British Heart Foundation Centre, King's College London, London, UK.
authors.forename: Renata S M
authors.initials: RS
authors.lastname: Gomes
authors.affiliation: King's British Heart Foundation Centre, King's College London, London, UK.
authors.forename: Philipp
authors.initials: P
authors.lastname: Skroblin
authors.affiliation: King's British Heart Foundation Centre, King's College London, London, UK.
authors.forename: Alex B
authors.initials: AB
authors.lastname: Munster
authors.affiliation: King's British Heart Foundation Centre, King's College London, London, UK.
authors.forename: Hannah
authors.initials: H
authors.lastname: Tomlins
authors.affiliation: King's British Heart Foundation Centre, King's College London, London, UK.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Langley
authors.affiliation: King's British Heart Foundation Centre, King's College London, London, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Zampetaki
authors.affiliation: King's British Heart Foundation Centre, King's College London, London, UK.
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Yin
authors.affiliation: Cardiovascular Development, Randall Division, King's College London, UK.
authors.forename: Fiona C
authors.initials: FC
authors.lastname: Wardle
authors.affiliation: King's British Heart Foundation Centre, King's College London, London, UK. Electronic address: manuel.mayr@kcl.ac.uk.
authors.forename: Manuel
authors.initials: M
authors.lastname: Mayr
mesh_terms: D000818:Animals; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000254:growth & development*; D006352:Heart Ventricles / Q000254:growth & development / Q000378:metabolism; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis; D008840:Microfilament Proteins / Q000096:biosynthesis; D009124:Muscle Proteins / Q000096:biosynthesis; D032383:Myocytes, Cardiac / Q000378:metabolism; D020543:Proteome / Q000096:biosynthesis* / Q000235:genetics; D040901:Proteomics; D012038:Regeneration / Q000235:genetics*; D059467:Transcriptome; D019210:Troponin I / Q000096:biosynthesis; D015027:Zebrafish / Q000235:genetics* / Q000254:growth & development
chemical_list: D035683:MicroRNAs; D008840:Microfilament Proteins; D009124:Muscle Proteins; C523647:Myoz1 protein, mouse; D020543:Proteome; D019210:Troponin I
keywords: Cardiomyocyte; Myofilament; Proteomics; Regeneration; Stem cell
references.citation: Circ Res. 2009 Jan 2;104(1):32-40
references.pmid: 19023133
references.citation: Anat Rec. 2001 Sep 1;264(1):1-12
references.pmid: 11505366
references.citation: Annu Rev Cell Dev Biol. 2012;28:719-41
references.pmid: 23057748
references.citation: BMC Evol Biol. 2013;13:142
references.pmid: 24059862
references.citation: Mol Cell Proteomics. 2013 Jun;12(6):1502-12
references.pmid: 23412571
references.citation: Nat Med. 2011 Jan;17(1):71-8
references.pmid: 21186368
references.citation: Comp Funct Genomics. 2003;4(6):609-25
references.pmid: 18629027
references.citation: Development. 2012 Jun;139(11):1921-30
references.pmid: 22513374
references.citation: J Proteomics. 2011 Dec 21;75(2):425-34
references.pmid: 21890006
references.citation: Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1595-600
references.pmid: 11171996
references.citation: J Am Coll Cardiol. 2015 Mar 10;65(9):892-900
references.pmid: 25618530
references.citation: Nature. 2015 Jul 9;523(7559):226-30
references.pmid: 26098368
references.citation: Circulation. 2011 Mar 29;123(12):1287-96
references.pmid: 21403094
references.citation: Science. 2011 Feb 25;331(6020):1078-80
references.pmid: 21350179
references.citation: Circ Cardiovasc Genet. 2010 Oct;3(5):426-35
references.pmid: 20733065