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The role of Metrn\u03b2 in cardiac disease is completely unknown. Here, we show that Metrn\u03b2-null mice exhibit asymmetrical cardiac hypertrophy, fibrosis, and enhanced signs of cardiac dysfunction in response to isoproterenol-induced cardiac hypertrophy and aging. Conversely, adeno-associated virus\u2013mediated specific overexpression of Metrn\u03b2 in the heart prevents the development of cardiac remodeling. Furthermore, Metrn\u03b2 inhibits cardiac hypertrophy development in cardiomyocytes in vitro, indicating a direct effect on cardiac cells. Antibody-mediated blockage of Metrn\u03b2 in cardiomyocyte cell cultures indicated an autocrine action of Metrn\u03b2 on the heart, in addition to an endocrine action. Moreover, Metrn\u03b2 is highly produced in the heart, and analysis of circulating Metrn\u03b2 concentrations in a large cohort of patients reveals that it is a new biomarker of heart failure with an independent prognostic value.<\/jats:p>","DOI":"10.1084\/jem.20201206","type":"journal-article","created":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T02:21:49Z","timestamp":1611886909000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":80,"title":["Meteorin-like\/Meteorin-\u03b2 protects heart against cardiac dysfunction"],"prefix":"10.1084","volume":"218","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6338-6420","authenticated-orcid":true,"given":"Celia","family":"Rup\u00e9rez","sequence":"first","affiliation":[{"name":"Departament de Bioqu\u00edmica i Biologia Molecular, Institut de Biomedicina, Universitat de Barcelona, Barcelona, Spain 1"},{"name":"2Centro de Investigaci\u00f3n Biom\u00e9dica en Red Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2651-649X","authenticated-orcid":true,"given":"Gemma","family":"Ferrer-Curriu","sequence":"additional","affiliation":[{"name":"Departament de Bioqu\u00edmica i Biologia Molecular, Institut de Biomedicina, Universitat de Barcelona, Barcelona, Spain 1"},{"name":"2Centro de Investigaci\u00f3n Biom\u00e9dica en Red Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3944-9756","authenticated-orcid":true,"given":"Aina","family":"Cervera-Barea","sequence":"additional","affiliation":[{"name":"Departament de Bioqu\u00edmica i Biologia Molecular, Institut de Biomedicina, Universitat de Barcelona, Barcelona, Spain 1"},{"name":"2Centro de Investigaci\u00f3n Biom\u00e9dica en Red Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1541-2203","authenticated-orcid":true,"given":"Laura","family":"Florit","sequence":"additional","affiliation":[{"name":"Departament de Bioqu\u00edmica i Biologia Molecular, Institut de Biomedicina, Universitat de Barcelona, Barcelona, Spain 1"},{"name":"2Centro de Investigaci\u00f3n Biom\u00e9dica en Red Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9768-4706","authenticated-orcid":true,"given":"Mariona","family":"Guitart-Mampel","sequence":"additional","affiliation":[{"name":"Muscle Research and Mitochondrial Function Laboratory, Cellex \u2013 August Pi i Sunyer Biomedical Research Institute, Faculty of Medicine and Health Science, University of Barcelona, Internal Medicine Service, Hospital Cl\u00ednic of Barcelona, Barcelona, Spain 3"},{"name":"4Center for Biomedical Research Network on Rare Diseases, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8973-9933","authenticated-orcid":true,"given":"Gloria","family":"Garrabou","sequence":"additional","affiliation":[{"name":"Muscle Research and Mitochondrial Function Laboratory, Cellex \u2013 August Pi i Sunyer Biomedical Research Institute, Faculty of Medicine and Health Science, University of Barcelona, Internal Medicine Service, Hospital Cl\u00ednic of Barcelona, Barcelona, Spain 3"},{"name":"4Center for Biomedical Research Network on Rare Diseases, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5376-5432","authenticated-orcid":true,"given":"M\u00f2nica","family":"Zamora","sequence":"additional","affiliation":[{"name":"Fetal I+D Fetal Medicine Research Center, BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clinic and Hospital San Juan de Deu), Institut Clinic de Ginecologia, Obstetricia i Neonatalogia, August Pi i Sunyer Biomedical Research Institute, University of Barcelona, Barcelona, Spain 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7422-5240","authenticated-orcid":true,"given":"F\u00e0tima","family":"Crispi","sequence":"additional","affiliation":[{"name":"Fetal I+D Fetal Medicine Research Center, BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clinic and Hospital San Juan de Deu), Institut Clinic de Ginecologia, Obstetricia i Neonatalogia, August Pi i Sunyer Biomedical Research Institute, University of Barcelona, Barcelona, Spain 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8180-8479","authenticated-orcid":true,"given":"Joaquim","family":"Fernandez-Sol\u00e0","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hospital Clinic, University of Barcelona, Barcelona, Spain 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5601-9611","authenticated-orcid":true,"given":"Josep","family":"Lup\u00f3n","sequence":"additional","affiliation":[{"name":"Heart Institute, Germans Trias i Pujol University Hospital, Center for Biomedical Research Network\u00a0on\u00a0Cardiovascular Diseases, Badalona, Spain 7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3044-197X","authenticated-orcid":true,"given":"Antoni","family":"Bayes-Genis","sequence":"additional","affiliation":[{"name":"Heart Institute, Germans Trias i Pujol University Hospital, Center for Biomedical Research Network\u00a0on\u00a0Cardiovascular Diseases, Badalona, Spain 7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1266-9142","authenticated-orcid":true,"given":"Francesc","family":"Villarroya","sequence":"additional","affiliation":[{"name":"Departament de Bioqu\u00edmica i Biologia Molecular, Institut de Biomedicina, Universitat de Barcelona, Barcelona, Spain 1"},{"name":"2Centro de Investigaci\u00f3n Biom\u00e9dica en Red Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5474-4724","authenticated-orcid":true,"given":"Anna","family":"Planavila","sequence":"additional","affiliation":[{"name":"Departament de Bioqu\u00edmica i Biologia Molecular, Institut de Biomedicina, Universitat de Barcelona, Barcelona, Spain 1"},{"name":"2Centro de Investigaci\u00f3n Biom\u00e9dica en Red Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2021,2,26]]},"reference":[{"key":"2026040611590810300_bib1","doi-asserted-by":"publisher","first-page":"21872","DOI":"10.1074\/jbc.M109.022749","article-title":"SIRT1 controls the transcription of the peroxisome proliferator-activated receptor-gamma co-activator-1alpha (PGC-1alpha) gene in skeletal muscle through the PGC-1alpha autoregulatory loop and interaction with MyoD","volume":"284","author":"Amat","year":"2009","journal-title":"J. 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