title: miR-133a enhances the protective capacity of cardiac progenitors cells after myocardial infarction.
abstract: miR-133a and miR-1 are known as muscle-specific microRNAs that are involved in cardiac development and pathophysiology. We have shown that both miR-1 and miR-133a are early and progressively upregulated during in vitro cardiac differentiation of adult cardiac progenitor cells (CPCs), but only miR-133a expression was enhanced under in vitro oxidative stress. miR-1 was demonstrated to favor differentiation of CPCs, whereas miR-133a overexpression protected CPCs against cell death, targeting, among others, the proapoptotic genes Bim and Bmf. miR-133a-CPCs clearly improved cardiac function in a rat myocardial infarction model by reducing fibrosis and hypertrophy and increasing vascularization and cardiomyocyte proliferation. The beneficial effects of miR-133a-CPCs seem to correlate with the upregulated expression of several relevant paracrine factors and the plausible cooperative secretion of miR-133a via exosomal transport. Finally, an in vitro heart muscle model confirmed the antiapoptotic effects of miR-133a-CPCs, favoring the structuration and contractile functionality of the artificial tissue.
authors.affiliation: Immunology and Oncology Department, National Center for Biotechnology, CSIC, 28049 Madrid, Spain; Department of Cardiovascular Development and Repair, Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, 28029 Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Izarra
authors.affiliation: Department of Cardiovascular Development and Repair, Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, 28029 Madrid, Spain; Cardiovascular Area, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, 15706 Santiago de Compostela, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Moscoso
authors.affiliation: Institute of Pharmacology, Heart Research Center Göttingen, University Medical Center, Georg-August University Göttingen and DZHK (German Center for Cardiovascular Research), 37075 Göttingen, Germany.
authors.forename: Elif
authors.initials: E
authors.lastname: Levent
authors.affiliation: Immunology and Oncology Department, National Center for Biotechnology, CSIC, 28049 Madrid, Spain; Department of Cardiovascular Development and Repair, Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, 28029 Madrid, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Cañón
authors.affiliation: Instituto de Investigación Sanitaria INCLIVA, 46010 Valencia, Spain; Unidad de Cardioregeneración, Hospital La Fe, 46009 Valencia, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Cerrada
authors.affiliation: Department of Cardiovascular Development and Repair, Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, 28029 Madrid, Spain; Instituto de Investigación Sanitaria INCLIVA, 46010 Valencia, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Díez-Juan
authors.affiliation: Department of Cardiovascular Development and Repair, Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, 28029 Madrid, Spain.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Blanca
authors.affiliation: Servicio de Cardiología, Hospital Clínico San Carlos, 28040 Madrid, Spain.
authors.forename: Iván-J
authors.initials: IJ
authors.lastname: Núñez-Gil
authors.affiliation: Department of Cardiovascular Development and Repair, Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, 28029 Madrid, Spain.
authors.forename: Iñigo
authors.initials: I
authors.lastname: Valiente
authors.affiliation: Departamento de Patología, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain.
authors.forename: Amparo
authors.initials: A
authors.lastname: Ruíz-Sauri
authors.affiliation: Instituto de Investigación Sanitaria INCLIVA, 46010 Valencia, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Sepúlveda
authors.affiliation: Institute of Pharmacology, Heart Research Center Göttingen, University Medical Center, Georg-August University Göttingen and DZHK (German Center for Cardiovascular Research), 37075 Göttingen, Germany.
authors.forename: Malte
authors.initials: M
authors.lastname: Tiburcy
authors.affiliation: Institute of Pharmacology, Heart Research Center Göttingen, University Medical Center, Georg-August University Göttingen and DZHK (German Center for Cardiovascular Research), 37075 Göttingen, Germany.
authors.forename: Wolfram-H
authors.initials: WH
authors.lastname: Zimmermann
authors.affiliation: Immunology and Oncology Department, National Center for Biotechnology, CSIC, 28049 Madrid, Spain; Department of Cardiovascular Development and Repair, Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, 28029 Madrid, Spain. Electronic address: abernad@cnb.csic.es.
authors.forename: Antonio
authors.initials: A
authors.lastname: Bernad
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000235:genetics / Q000473:pathology; D019295:Computational Biology; D015870:Gene Expression; D020869:Gene Expression Profiling; D035683:MicroRNAs / Q000235:genetics*; D032386:Myoblasts, Cardiac / Q000378:metabolism*; D009203:Myocardial Infarction / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats
chemical_list: C542191:MIRN1 microRNA, rat; C549446:MIRN133 microRNA, rat; D035683:MicroRNAs; D012333:RNA, Messenger