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Cell Rep. 2015 Sep 8;12(10):1691-703. doi: 10.1016/j.celrep.2015.07.064. Epub 2015 Aug 28.

Telomerase Is Essential for Zebrafish Heart Regeneration.

Author information

1
Regeneration and Aging Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC-ISCIII), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
2
Development of the Epicardium and Its Role during Regeneration Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC-ISCIII), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
3
Cardiovascular Imaging in Humans, Centro Nacional de Investigaciones Cardiovasculares (CNIC-ISCIII), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
4
Bioinformatic Unit, Centro Nacional de Investigaciones Cardiovasculares (CNIC-ISCIII), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
5
Electron Microscopy Center, Complutense University, Madrid 28040, Spain.
6
Development of the Epicardium and Its Role during Regeneration Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC-ISCIII), Melchor Fernández Almagro 3, 28029 Madrid, Spain. Electronic address: nmercader@cnic.es.
7
Regeneration and Aging Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC-ISCIII), Melchor Fernández Almagro 3, 28029 Madrid, Spain. Electronic address: iflores@cnic.es.

Abstract

After myocardial infarction in humans, lost cardiomyocytes are replaced by an irreversible fibrotic scar. In contrast, zebrafish hearts efficiently regenerate after injury. Complete regeneration of the zebrafish heart is driven by the strong proliferation response of its cardiomyocytes to injury. Here we show that, after cardiac injury in zebrafish, telomerase becomes hyperactivated, and telomeres elongate transiently, preceding a peak of cardiomyocyte proliferation and full organ recovery. Using a telomerase-mutant zebrafish model, we found that telomerase loss drastically decreases cardiomyocyte proliferation and fibrotic tissue regression after cryoinjury and that cardiac function does not recover. The impaired cardiomyocyte proliferation response is accompanied by the absence of cardiomyocytes with long telomeres and an increased proportion of cardiomyocytes showing DNA damage and senescence characteristics. These findings demonstrate the importance of telomerase function in heart regeneration and highlight the potential of telomerase therapy as a means of stimulating cell proliferation upon myocardial infarction.

PMID:
26321646
PMCID:
PMC4589159
DOI:
10.1016/j.celrep.2015.07.064
[Indexed for MEDLINE]
Free PMC Article
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