title: Telomerase Is Essential for Zebrafish Heart Regeneration.
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.
authors: Regeneration and Aging Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC-ISCIII), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
authors: Dorota
authors: D
authors: Bednarek
authors: Development of the Epicardium and Its Role during Regeneration Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC-ISCIII), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
authors: Juan Manuel
authors: JM
authors: González-Rosa
authors: Cardiovascular Imaging in Humans, Centro Nacional de Investigaciones Cardiovasculares (CNIC-ISCIII), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
authors: Gabriela
authors: G
authors: Guzmán-Martínez
authors: Regeneration and Aging Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC-ISCIII), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
authors: Óscar
authors: Ó
authors: Gutiérrez-Gutiérrez
authors: Regeneration and Aging Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC-ISCIII), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
authors: Tania
authors: T
authors: Aguado
authors: Regeneration and Aging Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC-ISCIII), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
authors: Carlota
authors: C
authors: Sánchez-Ferrer
authors: Development of the Epicardium and Its Role during Regeneration Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC-ISCIII), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
authors: Inês João
authors: IJ
authors: Marques
authors: Development of the Epicardium and Its Role during Regeneration Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC-ISCIII), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
authors: María
authors: M
authors: Galardi-Castilla
authors: Regeneration and Aging Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC-ISCIII), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
authors: Irene
authors: I
authors: de Diego
authors: Bioinformatic Unit, Centro Nacional de Investigaciones Cardiovasculares (CNIC-ISCIII), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
authors: Manuel José
authors: MJ
authors: Gómez
authors: Electron Microscopy Center, Complutense University, Madrid 28040, Spain.
authors: Alfonso
authors: A
authors: Cortés
authors: Electron Microscopy Center, Complutense University, Madrid 28040, Spain.
authors: Agustín
authors: A
authors: Zapata
authors: Cardiovascular Imaging in Humans, Centro Nacional de Investigaciones Cardiovasculares (CNIC-ISCIII), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
authors: Luis Jesús
authors: LJ
authors: Jiménez-Borreguero
authors: 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.
authors: Nadia
authors: N
authors: Mercader
authors: Regeneration and Aging Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC-ISCIII), Melchor Fernández Almagro 3, 28029 Madrid, Spain. Electronic address: iflores@cnic.es.
authors: Ignacio
authors: I
authors: Flores
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D015870:Gene Expression; D055786:Gene Knockout Techniques; D006321:Heart / Q000502:physiology*; D009206:Myocardium / Q000201:enzymology; D032383:Myocytes, Cardiac / Q000502:physiology; D012038:Regeneration; D019098:Telomerase / Q000502:physiology*; D046509:Tissue Culture Techniques; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000502:physiology*
chemical_list: D029961:Zebrafish Proteins; D019098:Telomerase