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Extensive scar formation and regression during heart regeneration after cryoinjury in zebrafish

González-Rosa, Juan Manuel, Martín, Víctor, Peralta, Marina, Torres, Miguel, Mercader, Nadia·2011·Development

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.

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Crossref · 10.1242/dev.060897

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Metadata

Authors
González-Rosa, J. M., Martín, V., Peralta, M., Torres, M., & Mercader, N.
Venue
Development
Published
2011-05-01
Volume
138
Issue
9
Pages
1663-1674
ISSN
  • 0950-1991 (ISSN-L)
  • 1477-9129
OpenAlex
W2022287530
Cited by
468
References
3
FWCI
9.64
Type
journal article
Language
en
Open access
closed

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