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Nat Commun. 2014 Dec 18;5:5863. doi: 10.1038/ncomms6863.

Telomerase expression confers cardioprotection in the adult mouse heart after acute myocardial infarction.

Author information

1
Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3, E-28029 Madrid, Spain.
2
Centre of Animal Biotechnology and Gene Therapy (CBATEG), Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Universitat Autónoma de Barcelona, E-08193 Bellaterra, Spain.
3
Cardiovascular and Metabolism Disease Therapy Area, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland.
4
Histopathology Unit, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, E-28029 Madrid, Spain.
5
Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, E-28029 Madrid, Spain.
6
Molecular Imaging Unit, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, E-28029 Madrid, Spain.
7
Molekulare und Translationale Kardiologie, Hans-Borst-Zentrum fuür Herzund Stammzellforschung, Klinik fuür Kardiologie und Angiologie, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany.
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Contributed equally

Abstract

Coronary heart disease is one of the main causes of death in the developed world, and treatment success remains modest, with high mortality rates within 1 year after myocardial infarction (MI). Thus, new therapeutic targets and effective treatments are necessary. Short telomeres are risk factors for age-associated diseases, including heart disease. Here we address the potential of telomerase (Tert) activation in prevention of heart failure after MI in adult mice. We use adeno-associated viruses for cardiac-specific Tert expression. We find that upon MI, hearts expressing Tert show attenuated cardiac dilation, improved ventricular function and smaller infarct scars concomitant with increased mouse survival by 17% compared with controls. Furthermore, Tert treatment results in elongated telomeres, increased numbers of Ki67 and pH3-positive cardiomyocytes and a gene expression switch towards a regeneration signature of neonatal mice. Our work suggests telomerase activation could be a therapeutic strategy to prevent heart failure after MI.

PMID:
25519492
PMCID:
PMC4871230
DOI:
10.1038/ncomms6863
[Indexed for MEDLINE]
Free PMC Article
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