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

Christian Bär, Bruno Bernardes de Jesus, Rosa Serrano, Agueda Tejera, Eduard Ayuso, Veronica Jimenez, Ivan Formentini, Maria Bobadilla, Jacques Mizrahi, Alba de Martino, Gonzalo Gomez, David Pisano, Francisca Mulero, Kai C. Wollert, Fatima Bosch and Maria A. Blasco ()
Additional contact information
Christian Bär: Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO)
Bruno Bernardes de Jesus: Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO)
Rosa Serrano: Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO)
Agueda Tejera: Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO)
Eduard Ayuso: Centre of Animal Biotechnology and Gene Therapy (CBATEG), School of Veterinary Medicine, Universitat Autònoma de Barcelona
Veronica Jimenez: Centre of Animal Biotechnology and Gene Therapy (CBATEG), School of Veterinary Medicine, Universitat Autònoma de Barcelona
Ivan Formentini: Cardiovascular and Metabolism Disease Therapy Area, F. Hoffmann-La Roche Ltd
Maria Bobadilla: Cardiovascular and Metabolism Disease Therapy Area, F. Hoffmann-La Roche Ltd
Jacques Mizrahi: Cardiovascular and Metabolism Disease Therapy Area, F. Hoffmann-La Roche Ltd
Alba de Martino: Histopathology Unit, Spanish National Cancer Research Centre (CNIO)
Gonzalo Gomez: Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO)
David Pisano: Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO)
Francisca Mulero: Molecular Imaging Unit, Spanish National Cancer Research Centre (CNIO)
Kai C. Wollert: Molekulare und Translationale Kardiologie, Hans-Borst-Zentrum fuür Herz- und Stammzellforschung, Klinik fuür Kardiologie und Angiologie, Medizinische Hochschule Hannover
Fatima Bosch: Centre of Animal Biotechnology and Gene Therapy (CBATEG), School of Veterinary Medicine, Universitat Autònoma de Barcelona
Maria A. Blasco: Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO)

Nature Communications, 2014, vol. 5, issue 1, 1-14

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms6863

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