{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T15:13:36Z","timestamp":1786979616280,"version":"build-2736575974"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2016,11,26]],"date-time":"2016-11-26T00:00:00Z","timestamp":1480118400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,11,26]],"date-time":"2016-11-26T00:00:00Z","timestamp":1480118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["StG282078"],"award-info":[{"award-number":["StG282078"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL062881"],"award-info":[{"award-number":["R01HL062881"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Mol Med"],"published-print":{"date-parts":[[2016,12]]},"DOI":"10.1007\/s00109-016-1483-3","type":"journal-article","created":{"date-parts":[[2016,11,26]],"date-time":"2016-11-26T03:32:55Z","timestamp":1480131175000},"page":"1349-1358","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Reducing RBM20 activity improves diastolic dysfunction and cardiac atrophy"],"prefix":"10.1007","volume":"94","author":[{"given":"Florian","family":"Hinze","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Dieterich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Radke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henk","family":"Granzier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1788-3172","authenticated-orcid":false,"given":"Michael","family":"Gotthardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,11,26]]},"reference":[{"key":"1483_CR1","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1056\/NEJMoa1406656","volume":"372","author":"GA Roth","year":"2015","unstructured":"Roth GA, Forouzanfar MH, Moran AE, Barber R, Nguyen G, Feigin VL, Naghavi M, Mensah GA, Murray CJL (2015) Demographic and epidemiologic drivers of global cardiovascular mortality. N Engl J Med 372:1333\u20131341","journal-title":"N Engl J Med"},{"key":"1483_CR2","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1038\/nm.2693","volume":"18","author":"W Guo","year":"2012","unstructured":"Guo W, Schafer S, Greaser ML, Radke MH, Liss M, Govindarajan T, Maatz H, Schulz H, Li S, Parrish AM et al (2012) RBM20, a gene for hereditary cardiomyopathy, regulates titin splicing. Nat Med 18:766\u2013773","journal-title":"Nat Med"},{"key":"1483_CR3","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1161\/01.RES.0000115522.52554.86","volume":"94","author":"S Lahmers","year":"2004","unstructured":"Lahmers S, Wu Y, Call DR, Labeit S, Granzier H (2004) Developmental control of titin isoform expression and passive stiffness in fetal and neonatal myocardium. Circ Res 94:505\u2013513","journal-title":"Circ Res"},{"key":"1483_CR4","first-page":"708","volume":"95","author":"I Makarenko","year":"2004","unstructured":"Makarenko I, Opitz CA, Leake MC, Neagoe C, Kulke M, Gwathmey JK, del M F, Hajjar RJ, Linke WA (2004) Passive stiffness changes caused by upregulation of compliant titin isoforms in human dilated cardiomyopathy hearts. CircRes 95:708\u2013716","journal-title":"CircRes"},{"key":"1483_CR5","doi-asserted-by":"publisher","first-page":"3444","DOI":"10.1073\/pnas.0608543104","volume":"104","author":"MH Radke","year":"2007","unstructured":"Radke MH, Peng J, Wu Y, McNabb M, Nelson OL, Granzier H, Gotthardt M (2007) Targeted deletion of titin N2B region leads to diastolic dysfunction and cardiac atrophy. ProcNatlAcadSciUSA 104:3444\u20133449","journal-title":"ProcNatlAcadSciUSA"},{"key":"1483_CR6","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1161\/CIRCRESAHA.109.200964","volume":"105","author":"HL Granzier","year":"2009","unstructured":"Granzier HL, Radke MH, Peng J, Westermann D, Nelson OL, Rost K, King NMP, Yu Q, Tsch\u00f6pe C, McNabb M et al (2009) Truncation of titin\u2019s elastic PEVK region leads to cardiomyopathy with diastolic dysfunction. Circ Res 105:557\u2013564","journal-title":"Circ Res"},{"key":"1483_CR7","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1016\/j.yjmcc.2010.05.006","volume":"49","author":"E-J Lee","year":"2010","unstructured":"Lee E-J, Peng J, Radke M, Gotthardt M, Granzier HL (2010) Calcium sensitivity and the frank-Starling mechanism of the heart are increased in titin N2B region-deficient mice. J Mol Cell Cardiol 49:449\u2013458","journal-title":"J Mol Cell Cardiol"},{"key":"1483_CR8","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.1016\/j.bpj.2011.06.054","volume":"101","author":"J Nedrud","year":"2011","unstructured":"Nedrud J, Labeit S, Gotthardt M, Granzier H (2011) Mechanics on myocardium deficient in the N2B region of titin: the cardiac-unique spring element improves efficiency of the cardiac cycle. Biophys J 101:1385\u20131392","journal-title":"Biophys J"},{"key":"1483_CR9","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1016\/j.jacc.2009.05.038","volume":"54","author":"KM Brauch","year":"2009","unstructured":"Brauch KM, Karst ML, Herron KJ, de Andrade M, Pellikka PA, Rodeheffer RJ, Michels VV, Olson TM (2009) Mutations in ribonucleic acid binding protein gene cause familial dilated cardiomyopathy. J Am Coll Cardiol 54:930\u2013941","journal-title":"J Am Coll Cardiol"},{"key":"1483_CR10","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1016\/j.hrthm.2011.10.016","volume":"9","author":"MM Refaat","year":"2012","unstructured":"Refaat MM, Lubitz SA, Makino S, Islam Z, Frangiskakis JM, Mehdi H, Gutmann R, Zhang ML, Bloom HL, Macrae CA et al (2012) Genetic variation in the alternative splicing regulator RBM20 is associated with dilated cardiomyopathy. Heart Rhythm Off J Heart Rhythm Soc 9:390\u2013396","journal-title":"Heart Rhythm Off J Heart Rhythm Soc"},{"key":"1483_CR11","doi-asserted-by":"publisher","first-page":"1924","DOI":"10.1161\/CIRCULATIONAHA.113.005610","volume":"129","author":"M Methawasin","year":"2014","unstructured":"Methawasin M, Hutchinson KR, Lee E-J, Smith JE, Saripalli C, Hidalgo CG, Ottenheijm CAC, Granzier H (2014) Experimentally increasing titin compliance in a novel mouse model attenuates the frank-Starling mechanism but has a beneficial effect on diastole. Circulation 129:1924\u20131936","journal-title":"Circulation"},{"key":"1483_CR12","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1161\/01.CIR.0000135591.37759.AF","volume":"110","author":"SF Nagueh","year":"2004","unstructured":"Nagueh SF, Shah G, Wu Y, Torre-Amione G, King NMP, Lahmers S, Witt CC, Becker K, Labeit S, Granzier HL (2004) Altered titin expression, myocardial stiffness, and left ventricular function in patients with dilated cardiomyopathy. Circulation 110:155\u2013162","journal-title":"Circulation"},{"key":"1483_CR13","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.1002\/elps.200305392","volume":"24","author":"CM Warren","year":"2003","unstructured":"Warren CM, Krzesinski PR, Greaser ML (2003) Vertical agarose gel electrophoresis and electroblotting of high-molecular-weight proteins. Electrophoresis 24:1695\u20131702","journal-title":"Electrophoresis"},{"key":"1483_CR14","doi-asserted-by":"publisher","first-page":"3419","DOI":"10.1172\/JCI74523","volume":"124","author":"H Maatz","year":"2014","unstructured":"Maatz H, Jens M, Liss M, Schafer S, Heinig M, Kirchner M, Adami E, Rintisch C, Dauksaite V, Radke MH et al (2014) RNA-binding protein RBM20 represses splicing to orchestrate cardiac pre-mRNA processing. J Clin Invest 124:3419\u20133430","journal-title":"J Clin Invest"},{"key":"1483_CR15","doi-asserted-by":"publisher","first-page":"3870","DOI":"10.1172\/JCI34472","volume":"118","author":"F Sheikh","year":"2008","unstructured":"Sheikh F, Raskin A, Chu P-H, Lange S, Domenighetti AA, Zheng M, Liang X, Zhang T, Yajima T, Gu Y et al (2008) An FHL1-containing complex within the cardiomyocyte sarcomere mediates hypertrophic biomechanical stress responses in mice. J Clin Invest 118:3870\u20133880","journal-title":"J Clin Invest"},{"key":"1483_CR16","doi-asserted-by":"publisher","first-page":"4925","DOI":"10.1242\/jcs.00181","volume":"115","author":"S Lange","year":"2002","unstructured":"Lange S, Auerbach D, McLoughlin P, Perriard E, Sch\u00e4fer BW, Perriard J-C, Ehler E (2002) Subcellular targeting of metabolic enzymes to titin in heart muscle may be mediated by DRAL\/FHL-2. J Cell Sci 115:4925\u20134936","journal-title":"J Cell Sci"},{"key":"1483_CR17","doi-asserted-by":"publisher","first-page":"129","DOI":"10.2147\/VHRM.S83662","volume":"12","author":"M Kanwar","year":"2016","unstructured":"Kanwar M, Walter C, Clarke M, Patarroyo-Aponte M (2016) Targeting heart failure with preserved ejection fraction: current status and future prospects. Vasc Health Risk Manag 12:129\u2013141","journal-title":"Vasc Health Risk Manag"},{"key":"1483_CR18","doi-asserted-by":"publisher","first-page":"2456","DOI":"10.1056\/NEJMoa0805450","volume":"359","author":"BM Massie","year":"2008","unstructured":"Massie BM, Carson PE, McMurray JJ, Komajda M, McKelvie R, Zile MR, Anderson S, Donovan M, Iverson E, Staiger C et al (2008) Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med 359:2456\u20132467","journal-title":"N Engl J Med"},{"key":"1483_CR19","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1056\/NEJMoa1313731","volume":"370","author":"B Pitt","year":"2014","unstructured":"Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B, Clausell N, Desai AS, Diaz R, Fleg JL et al (2014) Spironolactone for heart failure with preserved ejection fraction. N Engl J Med 370:1383\u20131392","journal-title":"N Engl J Med"},{"key":"1483_CR20","doi-asserted-by":"publisher","first-page":"2314","DOI":"10.1056\/NEJMoa1510774","volume":"373","author":"MM Redfield","year":"2015","unstructured":"Redfield MM, Anstrom KJ, Levine JA, Koepp GA, Borlaug BA, Chen HH, LeWinter MM, Joseph SM, Shah SJ, Semigran MJ et al (2015) Isosorbide mononitrate in heart failure with preserved ejection fraction. N Engl J Med 373:2314\u20132324","journal-title":"N Engl J Med"},{"key":"1483_CR21","doi-asserted-by":"publisher","first-page":"29273","DOI":"10.1074\/jbc.M112.372839","volume":"287","author":"A Raskin","year":"2012","unstructured":"Raskin A, Lange S, Banares K, Lyon RC, Zieseniss A, Lee LK, Yamazaki KG, Granzier HL, Gregorio CC, McCulloch AD et al (2012) A novel mechanism involving four-and-a-half LIM domain protein-1 and extracellular signal-regulated kinase-2 regulates titin phosphorylation and mechanics. J Biol Chem 287:29273\u201329284","journal-title":"J Biol Chem"}],"container-title":["Journal of Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00109-016-1483-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00109-016-1483-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00109-016-1483-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,15]],"date-time":"2020-05-15T12:18:23Z","timestamp":1589545103000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00109-016-1483-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11,26]]},"references-count":21,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2016,12]]}},"alternative-id":["1483"],"URL":"https:\/\/doi.org\/10.1007\/s00109-016-1483-3","relation":{},"ISSN":["0946-2716","1432-1440"],"issn-type":[{"value":"0946-2716","type":"print"},{"value":"1432-1440","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,11,26]]},"assertion":[{"value":"15 August 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 October 2016","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 November 2016","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 November 2016","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors have declared that no conflict of interest exists.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}