title: Telomerase expression confers cardioprotection in the adult mouse heart after acute myocardial infarction.
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.
authors.affiliation: Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3, E-28029 Madrid, Spain.
authors.forename: Christian
authors.initials: C
authors.lastname: Bär
authors.affiliation: Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3, E-28029 Madrid, Spain.
authors.forename: Bruno
authors.initials: B
authors.lastname: Bernardes de Jesus
authors.affiliation: Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3, E-28029 Madrid, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Serrano
authors.affiliation: Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3, E-28029 Madrid, Spain.
authors.forename: Agueda
authors.initials: A
authors.lastname: Tejera
authors.affiliation: 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.
authors.forename: Eduard
authors.initials: E
authors.lastname: Ayuso
authors.affiliation: 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.
authors.forename: Veronica
authors.initials: V
authors.lastname: Jimenez
authors.affiliation: Cardiovascular and Metabolism Disease Therapy Area, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland.
authors.forename: Ivan
authors.initials: I
authors.lastname: Formentini
authors.affiliation: Cardiovascular and Metabolism Disease Therapy Area, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland.
authors.forename: Maria
authors.initials: M
authors.lastname: Bobadilla
authors.affiliation: Cardiovascular and Metabolism Disease Therapy Area, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland.
authors.forename: Jacques
authors.initials: J
authors.lastname: Mizrahi
authors.affiliation: Histopathology Unit, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, E-28029 Madrid, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: de Martino
authors.affiliation: Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, E-28029 Madrid, Spain.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Gomez
authors.affiliation: Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, E-28029 Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Pisano
authors.affiliation: Molecular Imaging Unit, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, E-28029 Madrid, Spain.
authors.forename: Francisca
authors.initials: F
authors.lastname: Mulero
authors.affiliation: 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.
authors.forename: Kai C
authors.initials: KC
authors.lastname: Wollert
authors.affiliation: 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.
authors.forename: Fatima
authors.initials: F
authors.lastname: Bosch
authors.affiliation: Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3, E-28029 Madrid, Spain.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Blasco
mesh_terms: D000818:Animals; D000229:Dependovirus / Q000235:genetics; D015870:Gene Expression; D020869:Gene Expression Profiling; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D057809:HEK293 Cells; D006333:Heart Failure / Q000517:prevention & control*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058977:Molecular Sequence Annotation; D009203:Myocardial Infarction / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D016615:Telomere / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020257:Ventricular Remodeling
chemical_list: D006657:Histones; D019394:Ki-67 Antigen; D019098:Telomerase; C509187:Tert protein, mouse