title: Persistent scarring and dilated cardiomyopathy suggest incomplete regeneration of the apex resected neonatal mouse myocardium--A 180 days follow up study.
abstract: Heart damage in mammals is generally considered to result in scar formation, whereas zebrafish completely regenerate their hearts following an intermediate and reversible state of fibrosis after apex resection (AR). Recently, using the AR procedure, one-day-old mice were suggested to have full capacity for cardiac regeneration as well. In contrast, using the same mouse model others have shown that the regeneration process is incomplete and that scarring still remains 21 days after AR. The present study tested the hypothesis that like in zebrafish, fibrosis in neonatal mammals could be an intermediate response before the onset of complete heart regeneration. Myocardial damage was performed by AR in postnatal day 1 C57BL/6 mice, and myocardial function and scarring assessed at day 180 using F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) and histology, respectively. AR mice exhibited decreased ejection fraction and wall motion with increased end-diastolic and systolic volumes compared to sham-operated mice. Scarring with collagen accumulation was still substantial, with increased heart size, while cardiomyocyte size was unaffected. In conclusion, these data thus show that apex resection in mice results in irreversible fibrosis and dilated cardiomyopathy suggesting that cardiac regeneration is limited in neonatal mammals and thus distinct from the regenerative capacity seen in zebrafish.
authors.affiliation: Laboratory of Molecular and Cellular Cardiology, Dep. of Clinical Biochemistry and Pharmacology, Odense University Hospital, Winsloewparken 21(3rd), 5000 Odense C, Denmark; Clinical Institute/University of Southern Denmark, 5000 Odense C, Denmark; The Danish Regenerative Center (danishcrm.com), Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark. Electronic address: dandersen@health.sdu.dk.
authors.forename: Ditte Caroline
authors.initials: DC
authors.lastname: Andersen
authors.affiliation: Laboratory of Molecular and Cellular Cardiology, Dep. of Clinical Biochemistry and Pharmacology, Odense University Hospital, Winsloewparken 21(3rd), 5000 Odense C, Denmark; The Danish Regenerative Center (danishcrm.com), Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark.
authors.forename: Charlotte Harken
authors.initials: CH
authors.lastname: Jensen
authors.affiliation: Department of Nuclear Medicine, Odense University Hospital, Odense C, Denmark.
authors.forename: Christina
authors.initials: C
authors.lastname: Baun
authors.affiliation: Department of Nuclear Medicine, Odense University Hospital, Odense C, Denmark.
authors.forename: Svend
authors.initials: S
authors.lastname: Hvidsten
authors.affiliation: Experimental Renal and Cardiovascular Research, Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 12, 91054 Erlangen, Germany.
authors.forename: David C
authors.initials: DC
authors.lastname: Zebrowski
authors.affiliation: Experimental Renal and Cardiovascular Research, Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 12, 91054 Erlangen, Germany.
authors.forename: Felix Benedikt
authors.initials: FB
authors.lastname: Engel
authors.affiliation: Laboratory of Molecular and Cellular Cardiology, Dep. of Clinical Biochemistry and Pharmacology, Odense University Hospital, Winsloewparken 21(3rd), 5000 Odense C, Denmark; Institute of Molecular Medicine, University of Southern Denmark, 5000 Odense C, Denmark; The Danish Regenerative Center (danishcrm.com), Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark. Electronic address: soeren.sheikh@rsyd.dk.
authors.forename: Søren Paludan
authors.initials: SP
authors.lastname: Sheikh
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure; D002311:Cardiomyopathy, Dilated / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology*; D049109:Cell Proliferation; D048429:Cell Size; D002921:Cicatrix / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology*; D005355:Fibrosis; D019788:Fluorodeoxyglucose F18; D006335:Heart Injuries / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000473:pathology; D049268:Positron-Emission Tomography; D012038:Regeneration / Q000502:physiology; D013045:Species Specificity; D013318:Stroke Volume; D015027:Zebrafish
chemical_list: D019788:Fluorodeoxyglucose F18
keywords: Apex resection; Fibrosis; Function; Heart; Neonatal; Regeneration