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

doi:10.1038/ncomms6863

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

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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 language	English
Article number	6863
Journal	Nature Communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms6863
Publication status	Published - 1 Jan 2014

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Bär, C., De Jesus, B. B., Serrano, R., Tejera, A., Ayuso, E., Jimenez, V., Formentini, I., Bobadilla, M., Mizrahi, J., De Martino, A., Gomez, G., Pisano, D., Mulero, F., Wollert, K. C., Bosch, F., & Blasco, M. A. (2014). Telomerase expression confers cardioprotection in the adult mouse heart after acute myocardial infarction. Nature Communications, 5, [6863]. https://doi.org/10.1038/ncomms6863

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title = "Telomerase expression confers cardioprotection in the adult mouse heart after acute myocardial infarction",

abstract = "{\textcopyright} 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.",

author = "Christian B{\"a}r and {De Jesus}, {Bruno Bernardes} and Rosa Serrano and Agueda Tejera and Eduard Ayuso and Veronica Jimenez and Ivan Formentini and Maria Bobadilla and Jacques Mizrahi and {De Martino}, Alba and Gonzalo Gomez and David Pisano and Francisca Mulero and Wollert, {Kai C.} and Fatima Bosch and Blasco, {Maria A.}",

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Bär, C, De Jesus, BB, Serrano, R, Tejera, A, Ayuso, E, Jimenez, V, Formentini, I, Bobadilla, M, Mizrahi, J, De Martino, A, Gomez, G, Pisano, D, Mulero, F, Wollert, KC, Bosch, F & Blasco, MA 2014, 'Telomerase expression confers cardioprotection in the adult mouse heart after acute myocardial infarction', Nature Communications, vol. 5, 6863. https://doi.org/10.1038/ncomms6863

TY - JOUR

T1 - Telomerase expression confers cardioprotection in the adult mouse heart after acute myocardial infarction

AU - Bär, Christian

AU - De Jesus, Bruno Bernardes

AU - Serrano, Rosa

AU - Tejera, Agueda

AU - Ayuso, Eduard

AU - Jimenez, Veronica

AU - Formentini, Ivan

AU - Bobadilla, Maria

AU - Mizrahi, Jacques

AU - De Martino, Alba

AU - Gomez, Gonzalo

AU - Pisano, David

AU - Mulero, Francisca

AU - Wollert, Kai C.

AU - Bosch, Fatima

AU - Blasco, Maria A.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - © 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.

AB - © 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.

U2 - 10.1038/ncomms6863

DO - 10.1038/ncomms6863

M3 - Article

VL - 5

M1 - 6863

ER -

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

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