{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T08:56:55Z","timestamp":1765357015636,"version":"build-2065373602"},"reference-count":50,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T00:00:00Z","timestamp":1634256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research, Development and Innovation Fund of Hungary, \u2019National Heart Program\u2019","award":["NVKP_16-1\u20132016-0017"],"award-info":[{"award-number":["NVKP_16-1\u20132016-0017"]}]},{"name":"Thematic Excellence Programme of the Ministry for Innovation and Technology in Hungary, within the framework of the Therapeutic Development and Bioimaging thematic programs of the Semmelweis University","award":["2020-4.1.1.-TKP2020"],"award-info":[{"award-number":["2020-4.1.1.-TKP2020"]}]},{"name":"New National Excellence Program of The Ministry for Innovation and Technology","award":["\u00daNKP-19-3-I (D.K.), \u00daNKP-21-3-II-SE-36 (B.K.)"],"award-info":[{"award-number":["\u00daNKP-19-3-I (D.K.), \u00daNKP-21-3-II-SE-36 (B.K.)"]}]},{"name":"Hungarian National Research, Development and Innovation Office","award":["K135360 (M.K.), K135076 (B.M.)"],"award-info":[{"award-number":["K135360 (M.K.), K135076 (B.M.)"]}]},{"name":"J\u00e1nos Bolyai Research Scholarship of the Hungarian Academy of Sciences.","award":["- (A.O.)"],"award-info":[{"award-number":["- (A.O.)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Long-term exercise induces physiological cardiac adaptation, a condition referred to as athlete\u2019s heart. Exercise tolerance is known to be associated with decreased cardiac passive stiffness. Passive stiffness of the heart muscle is determined by the giant elastic protein titin. The adult cardiac muscle contains two titin isoforms: the more compliant N2BA and the stiffer N2B. Titin-based passive stiffness may be controlled by altering the expression of the different isoforms or via post-translational modifications such as phosphorylation. Currently, there is very limited knowledge about titin\u2019s role in cardiac adaptation during long-term exercise. Our aim was to determine the N2BA\/N2B ratio and post-translational phosphorylation of titin in the left ventricle and to correlate the changes with the structure and transverse stiffness of cardiac sarcomeres in a rat model of an athlete\u2019s heart. The athlete\u2019s heart was induced by a 12-week-long swim-based training. In the exercised myocardium the N2BA\/N2B ratio was significantly increased, Ser11878 of the PEVK domain was hypophosphorlyated, and the sarcomeric transverse elastic modulus was reduced. Thus, the reduced passive stiffness in the athlete\u2019s heart is likely caused by a shift towards the expression of the longer cardiac titin isoform and a phosphorylation-induced softening of the PEVK domain which is manifested in a mechanical rearrangement locally, within the cardiac sarcomere.<\/jats:p>","DOI":"10.3390\/ijms222011110","type":"journal-article","created":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T13:35:47Z","timestamp":1634304947000},"page":"11110","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Increased Expression of N2BA Titin Corresponds to More Compliant Myofibrils in Athlete\u2019s Heart"],"prefix":"10.3390","volume":"22","author":[{"given":"Dalma","family":"Kellermayer","sequence":"first","affiliation":[{"name":"Heart and Vascular Center, Semmelweis University, V\u00e1rosmajor Str. 68., HU-1122 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e1lint","family":"Kiss","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Radiation Biology, Semmelweis University, T\u0171zolt\u00f3 Str. 37\u201347, HU-1094 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0875-5569","authenticated-orcid":false,"given":"Hedvig","family":"Tordai","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Radiation Biology, Semmelweis University, T\u0171zolt\u00f3 Str. 37\u201347, HU-1094 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Attila","family":"Ol\u00e1h","sequence":"additional","affiliation":[{"name":"Heart and Vascular Center, Semmelweis University, V\u00e1rosmajor Str. 68., HU-1122 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9516-407X","authenticated-orcid":false,"given":"Henk L.","family":"Granzier","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, University of Arizona, 1656 E Mabel Str., Tucson, AZ 85724-5217, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e9la","family":"Merkely","sequence":"additional","affiliation":[{"name":"Heart and Vascular Center, Semmelweis University, V\u00e1rosmajor Str. 68., HU-1122 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikl\u00f3s","family":"Kellermayer","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Radiation Biology, Semmelweis University, T\u0171zolt\u00f3 Str. 37\u201347, HU-1094 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tam\u00e1s","family":"Radovits","sequence":"additional","affiliation":[{"name":"Heart and Vascular Center, Semmelweis University, V\u00e1rosmajor Str. 68., HU-1122 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e002487","DOI":"10.1161\/CIRCIMAGING.114.002487","article-title":"Myocardial adaptations to recreational marathon training among middle-aged men","volume":"8","author":"Zilinski","year":"2015","journal-title":"Circ. 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