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, Maria A. Blasco

Research output: Contribution to journalArticleResearchpeer-review

77 Citations (Scopus)

Abstract

© 2014 Macmillan Publishers Limited. All rights reserved. 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.
Original languageEnglish
Article number6863
JournalNature Communications
Volume5
DOIs
Publication statusPublished - 1 Jan 2014

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