{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T01:57:49Z","timestamp":1791165469747,"version":"4.1.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2014,7,7]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale<\/jats:underline>\n              :\n            <\/jats:title>\n            <jats:p>Myostatin is a major negative regulator of skeletal muscle mass and initiates multiple metabolic changes, including enhanced insulin sensitivity. However, the function of myostatin in the heart is barely understood, although it is upregulated in the myocardium under several pathological conditions.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective<\/jats:underline>\n              :\n            <\/jats:title>\n            <jats:p>Here, we aimed to decipher the role of myostatin and myostatin-dependent signaling pathways for cardiac function and cardiac metabolism in adult mice. To avoid potential counterregulatory mechanisms occurring in constitutive and germ-line\u2013based myostatin mutants, we generated a mouse model that allows myostatin inactivation in adult cardiomyocytes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results<\/jats:underline>\n              :\n            <\/jats:title>\n            <jats:p>Cardiac MRI revealed that genetic inactivation of myostatin signaling in the adult murine heart caused cardiac hypertrophy and heart failure, partially recapitulating effects of the age-dependent decline of the myostatin paralog growth and differentiation factor 11. We found that myostatin represses AMP-activated kinase activation in the heart via transforming growth factor-\u03b2\u2013activated kinase 1, thereby preventing a metabolic switch toward glycolysis and glycogen accumulation. Furthermore, myostatin stimulated expression of regulator of G-protein signaling 2, a GTPase-activating protein that restricts Gaq and Gas signaling and thereby protects against cardiac failure. Inhibition of AMP-activated kinase in vivo rescued cardiac hypertrophy and prevented enhanced glycolytic flow and glycogen accumulation after inactivation of myostatin in cardiomyocytes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions<\/jats:underline>\n              :\n            <\/jats:title>\n            <jats:p>Our results uncover an important role of myostatin in the heart for maintaining cardiac energy homeostasis and preventing cardiac hypertrophy.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.115.304185","type":"journal-article","created":{"date-parts":[[2014,5,8]],"date-time":"2014-05-08T01:53:05Z","timestamp":1399513985000},"page":"296-310","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":96,"title":["Myostatin Regulates Energy Homeostasis in the Heart and Prevents Heart Failure"],"prefix":"10.1161","volume":"115","author":[{"given":"Nadine","family":"Biesemann","sequence":"first","affiliation":[{"name":"From the Department of Cardiac Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (N.B., L.M., A.W., M.K., T. Boettger, T. Borchardt, T. Braun); Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany (N.B.); Institute of Biochemistry, Faculty of General Medicine, University of Szeged, Szeged, Hungary (L.M.); and European Institute for Molecular Imaging, University of M\u00fcnster, M\u00fcnster, Germany (S.H., M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Mendler","sequence":"additional","affiliation":[{"name":"From the Department of Cardiac Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (N.B., L.M., A.W., M.K., T. Boettger, T. Borchardt, T. Braun); Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany (N.B.); Institute of Biochemistry, Faculty of General Medicine, University of Szeged, Szeged, Hungary (L.M.); and European Institute for Molecular Imaging, University of M\u00fcnster, M\u00fcnster, Germany (S.H., M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Wietelmann","sequence":"additional","affiliation":[{"name":"From the Department of Cardiac Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (N.B., L.M., A.W., M.K., T. Boettger, T. Borchardt, T. Braun); Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany (N.B.); Institute of Biochemistry, Faculty of General Medicine, University of Szeged, Szeged, Hungary (L.M.); and European Institute for Molecular Imaging, University of M\u00fcnster, M\u00fcnster, Germany (S.H., M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Hermann","sequence":"additional","affiliation":[{"name":"From the Department of Cardiac Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (N.B., L.M., A.W., M.K., T. Boettger, T. Borchardt, T. Braun); Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany (N.B.); Institute of Biochemistry, Faculty of General Medicine, University of Szeged, Szeged, Hungary (L.M.); and European Institute for Molecular Imaging, University of M\u00fcnster, M\u00fcnster, Germany (S.H., M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Sch\u00e4fers","sequence":"additional","affiliation":[{"name":"From the Department of Cardiac Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (N.B., L.M., A.W., M.K., T. Boettger, T. Borchardt, T. Braun); Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany (N.B.); Institute of Biochemistry, Faculty of General Medicine, University of Szeged, Szeged, Hungary (L.M.); and European Institute for Molecular Imaging, University of M\u00fcnster, M\u00fcnster, Germany (S.H., M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Kr\u00fcger","sequence":"additional","affiliation":[{"name":"From the Department of Cardiac Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (N.B., L.M., A.W., M.K., T. Boettger, T. Borchardt, T. Braun); Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany (N.B.); Institute of Biochemistry, Faculty of General Medicine, University of Szeged, Szeged, Hungary (L.M.); and European Institute for Molecular Imaging, University of M\u00fcnster, M\u00fcnster, Germany (S.H., M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Boettger","sequence":"additional","affiliation":[{"name":"From the Department of Cardiac Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (N.B., L.M., A.W., M.K., T. Boettger, T. Borchardt, T. Braun); Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany (N.B.); Institute of Biochemistry, Faculty of General Medicine, University of Szeged, Szeged, Hungary (L.M.); and European Institute for Molecular Imaging, University of M\u00fcnster, M\u00fcnster, Germany (S.H., M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thilo","family":"Borchardt","sequence":"additional","affiliation":[{"name":"From the Department of Cardiac Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (N.B., L.M., A.W., M.K., T. Boettger, T. Borchardt, T. Braun); Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany (N.B.); Institute of Biochemistry, Faculty of General Medicine, University of Szeged, Szeged, Hungary (L.M.); and European Institute for Molecular Imaging, University of M\u00fcnster, M\u00fcnster, Germany (S.H., M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Braun","sequence":"additional","affiliation":[{"name":"From the Department of Cardiac Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (N.B., L.M., A.W., M.K., T. Boettger, T. Borchardt, T. Braun); Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany (N.B.); Institute of Biochemistry, Faculty of General Medicine, University of Szeged, Szeged, Hungary (L.M.); and European Institute for Molecular Imaging, University of M\u00fcnster, M\u00fcnster, Germany (S.H., M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.23.12457"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2008-0003"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.2174\/187152210793663810"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0213562"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(199907)180:1<1::AID-JCP1>3.0.CO;2-V"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M201462200"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.2006.01718.x"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfq039"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(98)00205-6"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.04.015"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000231290.45676.d4"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2007.01.011"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2009.172544"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-11-0455"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.109.882068"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00107.2003"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1677\/JOE-07-0072"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2011.01.015"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvr071"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1999.9209"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M805301200"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00190.2012"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00129.2012"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.7.4.592"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.130708"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.17.6037-6048.2003"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0053743"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000258446.23525.37"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.20.012103.135836"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00329.2006"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81573-1"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.105.608968"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1000"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2010.03.015"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.26.14389"},{"key":"e_1_3_4_37_2","first-page":"408","article-title":"Regulator of G protein signaling 2 mediates cardiac compensation to pressure overload and antihypertrophic effects of PDE5 inhibition in mice.","volume":"119","author":"Takimoto E","year":"2009","unstructured":"Takimoto E, Koitabashi N, Hsu S, Ketner EA, Zhang M, Nagayama T, Bedja D, Gabrielson KL, Blanton R, Siderovski DP, Mendelsohn ME, Kass DA. 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