Extensive scar formation and regression during heart regeneration after cryoinjury in zebrafish
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TLDR
The results provide the first evidence that, like mammalian hearts, teleost hearts undergo massive fibrosis after cardiac damage, however, the fish heart can progressively eliminate the scar and regenerate the lost myocardium, indicating that scar formation is compatible with myocardial regeneration and the existence of endogenous mechanisms of scar regression.Abstract:
The zebrafish heart has the capacity to regenerate after ventricular resection. Although this regeneration model has proved useful for the elucidation of certain regeneration mechanisms, it is based on the removal of heart tissue rather than its damage. Here, we characterize the cellular response and regenerative capacity of the zebrafish heart after cryoinjury, an alternative procedure that more closely models the pathophysiological process undergone by the human heart after myocardial infarction (MI). Localized damage was induced in 25% of the ventricle by cryocauterization (CC). During the first 24 hours post-injury, CC leads to cardiomyocyte death within the injured area and the near coronary vasculature. Cell death is followed by a rapid proliferative response in endocardium, epicardium and myocardium. During the first 3 weeks post-injury cell debris was cleared and the injured area replaced by a massive scar. The fibrotic tissue was subsequently degraded and replaced by cardiac tissue. Although animals survived CC, their hearts showed nonhomogeneous ventricular contraction and had a thickened ventricular wall, suggesting that regeneration is associated with processes resembling mammalian ventricular remodeling after acute MI. Our results provide the first evidence that, like mammalian hearts, teleost hearts undergo massive fibrosis after cardiac damage. Unlike mammals, however, the fish heart can progressively eliminate the scar and regenerate the lost myocardium, indicating that scar formation is compatible with myocardial regeneration and the existence of endogenous mechanisms of scar regression. This finding suggests that CC-induced damage in zebrafish could provide a valuable model for the study of the mechanisms of scar removal post-MI.read more
Citations
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Regulation of neonatal and adult mammalian heart regeneration by the miR-15 family
Enzo R. Porrello,Ahmed I. Mahmoud,Emma Simpson,Brett A. Johnson,David Grinsfelder,Diana C. Canseco,Pradeep P.A. Mammen,Beverly A. Rothermel,Eric N. Olson,Hesham A. Sadek +9 more
TL;DR: It is concluded that the neonatal mammalian heart can regenerate after myocardial infarction through proliferation of preexisting cardiomyocytes and that the miR-15 family contributes to postnatal loss of cardiac regenerative capacity.
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The oxygen-rich postnatal environment induces cardiomyocyte cell-cycle arrest through DNA damage response.
Bao N. Puente,Wataru Kimura,Shalini Muralidhar,Jesung Moon,James F. Amatruda,Katherine J Phelps,David Grinsfelder,Beverly A. Rothermel,Rui Chen,Joseph A. Garcia,Celio X.C. Santos,Suwannee Thet,Eiichiro Mori,Michael Kinter,Paul M. Rindler,Serena Zacchigna,Shibani Mukherjee,David J. Chen,Ahmed I. Mahmoud,Mauro Giacca,Peter S. Rabinovitch,Asaithamby Aroumougame,Ajay M. Shah,Luke I. Szweda,Hesham A. Sadek +24 more
TL;DR: It is shown that reactive oxygen species (ROS), oxidative DNA damage, and DNA damage response (DDR) markers significantly increase in the heart during the first postnatal week, revealing a protective mechanism that mediates cardiomyocyte cell-cycle arrest in exchange for utilization of oxygen-dependent aerobic metabolism.
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The zebrafish as a model for complex tissue regeneration
TL;DR: Zebrafish studies have helped identify new mechanistic underpinnings of regeneration in multiple tissues and, in some cases, have served as a guide for contemplating regenerative strategies in mammals.
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Guidelines for experimental models of myocardial ischemia and infarction.
Merry L. Lindsey,Merry L. Lindsey,Roberto Bolli,John M. Canty,Xiao-Jun Du,Nikolaos G. Frangogiannis,Stefan Frantz,Robert G. Gourdie,Jeffrey W. Holmes,Steven P. Jones,Robert A. Kloner,Robert A. Kloner,David J. Lefer,Ronglih Liao,Elizabeth Murphy,Peipei Ping,Karin Przyklenk,Fabio A. Recchia,Fabio A. Recchia,Lisa Schwartz Longacre,Crystal M. Ripplinger,Jennifer E. Van Eyk,Gerd Heusch +22 more
TL;DR: The goal of this review is to provide best practice information regarding myocardial ischemia-reperfusion and infarction models and to provide increasing awareness of the need for rigor and reproducibility in designing and performing scientific research to ensure validation of results.
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The regenerative capacity of zebrafish reverses cardiac failure caused by genetic cardiomyocyte depletion
Jinhu Wang,Daniela Panáková,Kazu Kikuchi,Jennifer E. Holdway,Matthew Gemberling,James S. Burris,Sumeet Pal Singh,Amy L. Dickson,Yi-Fan Lin,M. Khaled Sabeh,Andreas A. Werdich,Deborah Yelon,Calum A. MacRae,Kenneth D. Poss +13 more
TL;DR: It is indicated that genetic depletion of cardiomyocytes, even at levels so extreme as to elicit signs of cardiac failure, can be reversed by natural regenerative capacity in lower vertebrates such as zebrafish.
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