{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:27:29Z","timestamp":1785421649136,"version":"3.56.0"},"reference-count":53,"publisher":"Rockefeller University Press","issue":"3","license":[{"start":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T00:00:00Z","timestamp":1741564800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/rupress.org\/pages\/terms102024"}],"funder":[{"DOI":"10.13039\/501100018818","name":"Hungarian National Research, Development and Innovation Office","doi-asserted-by":"publisher","award":["K135076"],"award-info":[{"award-number":["K135076"]}],"id":[{"id":"10.13039\/501100018818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018818","name":"Hungarian National Research, Development and Innovation Office","doi-asserted-by":"publisher","award":["K135360"],"award-info":[{"award-number":["K135360"]}],"id":[{"id":"10.13039\/501100018818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018818","name":"Hungarian National Research, Development and Innovation Office","doi-asserted-by":"publisher","award":["FK135462"],"award-info":[{"award-number":["FK135462"]}],"id":[{"id":"10.13039\/501100018818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018818","name":"Hungarian National Research, Development and Innovation Office","doi-asserted-by":"publisher","award":["FK145928"],"award-info":[{"award-number":["FK145928"]}],"id":[{"id":"10.13039\/501100018818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003825","name":"Hungarian Academy of Sciences","doi-asserted-by":"publisher","award":["BO\/00314\/24\/5"],"award-info":[{"award-number":["BO\/00314\/24\/5"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003825","name":"Hungarian Academy of Sciences","doi-asserted-by":"publisher","award":["BO\/00242\/24"],"award-info":[{"award-number":["BO\/00242\/24"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018818","name":"National Research, Development, and Innovation Fund","doi-asserted-by":"publisher","award":["\u00daNKP-19-3-I"],"award-info":[{"award-number":["\u00daNKP-19-3-I"]}],"id":[{"id":"10.13039\/501100018818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018818","name":"National Research, Development, and Innovation Fund","doi-asserted-by":"publisher","award":["\u00daNKP-23-3-II-SE-22"],"award-info":[{"award-number":["\u00daNKP-23-3-II-SE-22"]}],"id":[{"id":"10.13039\/501100018818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018818","name":"National Research, Development, and Innovation Fund","doi-asserted-by":"publisher","award":["TKP2021-EGA"],"award-info":[{"award-number":["TKP2021-EGA"]}],"id":[{"id":"10.13039\/501100018818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018818","name":"National Research, Development, and Innovation Fund","doi-asserted-by":"publisher","award":["TKP2021-NVA"],"award-info":[{"award-number":["TKP2021-NVA"]}],"id":[{"id":"10.13039\/501100018818","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Cardiovascular Laboratory","award":["RRF-2.3.1-21-2022-00003"],"award-info":[{"award-number":["RRF-2.3.1-21-2022-00003"]}]},{"DOI":"10.13039\/100020626","name":"Artificial Intelligence National Laboratory","doi-asserted-by":"publisher","award":["RRF-2.3.1-21-2022-00004"],"award-info":[{"award-number":["RRF-2.3.1-21-2022-00004"]}],"id":[{"id":"10.13039\/100020626","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Ministry of Innovation and Technology of Hungary","award":["TKP2021-EGA-23"],"award-info":[{"award-number":["TKP2021-EGA-23"]}]},{"name":"Ministry of Innovation and Technology of Hungary","award":["TKP2021-NVA-15"],"award-info":[{"award-number":["TKP2021-NVA-15"]}]},{"DOI":"10.13039\/100020916","name":"HUN-REN Hungarian Research Network","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020916","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,5,5]]},"abstract":"<jats:p>Marfan syndrome (MFS) is an autosomal dominant disease caused by mutations in the gene (FBN1) of fibrillin-1, a major determinant of the extracellular matrix (ECM). Functional impairment in the cardiac left ventricle (LV) of these patients is usually a consequence of aortic valve disease. However, LV passive stiffness may also be affected by chronic changes in mechanical load and ECM dysfunction. Passive stiffness is determined by the giant sarcomeric protein titin that has two main cardiac splice isoforms: the shorter and stiffer N2B and the longer and more compliant N2BA. Their ratio is thought to reflect myocardial response to pathologies. Whether this ratio and titin\u2019s sarcomeric layout is altered in MFS is currently unknown. Here, we studied LV samples from MFS patients carrying FBN1 mutation, collected during aortic root replacement surgery. We found that the N2BA:N2B titin ratio was elevated, indicating a shift toward the more compliant isoform. However, there were no alterations in the total titin content compared with healthy humans based on literature data. Additionally, while the gross sarcomeric structure was unaltered, the M-band was more extended in the MFS sarcomere. We propose that the elevated N2BA:N2B titin ratio reflects a general adaptation mechanism to the increased volume overload resulting from the valvular disease and the direct ECM disturbances so as to reduce myocardial passive stiffness and maintain diastolic function in MFS.<\/jats:p>","DOI":"10.1085\/jgp.202413690","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T02:20:32Z","timestamp":1737512432000},"update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Marfan syndrome cardiomyocytes show excess of titin isoform N2BA and extended sarcomeric M-band"],"prefix":"10.1085","volume":"157","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0398-0801","authenticated-orcid":true,"given":"Dalma","family":"Kellermayer","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01g9ty582","id-type":"ROR","asserted-by":"publisher"}],"name":"Semmelweis University 1 Department of Biophysics and Radiation Biology, , Budapest,","place":["Hungary"]},{"id":[{"id":"https:\/\/ror.org\/01g9ty582","id-type":"ROR","asserted-by":"publisher"}],"name":"Heart and Vascular Center, Semmelweis University 2 , Budapest,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5622-9136","authenticated-orcid":true,"given":"Cristina M.","family":"\u0218ulea","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01g9ty582","id-type":"ROR","asserted-by":"publisher"}],"name":"Semmelweis University 1 Department of Biophysics and Radiation Biology, , Budapest,","place":["Hungary"]},{"id":[{"id":"https:\/\/ror.org\/01g9ty582","id-type":"ROR","asserted-by":"publisher"}],"name":"Heart and Vascular Center, Semmelweis University 2 , Budapest,","place":["Hungary"]},{"name":"Hungarian Marfan Foundation 3 , Budapest,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0875-5569","authenticated-orcid":true,"given":"Hedvig","family":"Tordai","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01g9ty582","id-type":"ROR","asserted-by":"publisher"}],"name":"Semmelweis University 1 Department of Biophysics and Radiation Biology, , Budapest,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6363-4922","authenticated-orcid":true,"given":"K\u00e1lm\u00e1n","family":"Benke","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01g9ty582","id-type":"ROR","asserted-by":"publisher"}],"name":"Heart and Vascular Center, Semmelweis University 2 , Budapest,","place":["Hungary"]},{"name":"Hungarian Marfan Foundation 3 , Budapest,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7571-1478","authenticated-orcid":true,"given":"Mikl\u00f3s","family":"P\u00f3los","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01g9ty582","id-type":"ROR","asserted-by":"publisher"}],"name":"Heart and Vascular Center, Semmelweis University 2 , Budapest,","place":["Hungary"]},{"name":"Hungarian Marfan Foundation 3 , Budapest,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6492-0426","authenticated-orcid":true,"given":"Bence","family":"\u00c1gg","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01g9ty582","id-type":"ROR","asserted-by":"publisher"}],"name":"Heart and Vascular Center, Semmelweis University 2 , Budapest,","place":["Hungary"]},{"name":"Hungarian Marfan Foundation 3 , Budapest,","place":["Hungary"]},{"id":[{"id":"https:\/\/ror.org\/01g9ty582","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Pharmacology and Drug Research and Development, Department of Pharmacology and Pharmacotherapy, Semmelweis University 4 , Budapest,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6695-9877","authenticated-orcid":true,"given":"Roland","family":"Stengl","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01g9ty582","id-type":"ROR","asserted-by":"publisher"}],"name":"Heart and Vascular Center, Semmelweis University 2 , Budapest,","place":["Hungary"]},{"name":"Hungarian Marfan Foundation 3 , Budapest,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9346-3463","authenticated-orcid":true,"given":"M\u00e1t\u00e9","family":"Csonka","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01g9ty582","id-type":"ROR","asserted-by":"publisher"}],"name":"Heart and Vascular Center, Semmelweis University 2 , Budapest,","place":["Hungary"]},{"name":"Hungarian Marfan Foundation 3 , Budapest,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4090-776X","authenticated-orcid":true,"given":"Tam\u00e1s","family":"Radovits","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01g9ty582","id-type":"ROR","asserted-by":"publisher"}],"name":"Heart and Vascular Center, Semmelweis University 2 , Budapest,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6514-0723","authenticated-orcid":true,"given":"B\u00e9la","family":"Merkely","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01g9ty582","id-type":"ROR","asserted-by":"publisher"}],"name":"Heart and Vascular Center, Semmelweis University 2 , Budapest,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7628-7894","authenticated-orcid":true,"given":"Zolt\u00e1n","family":"Szabolcs","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01g9ty582","id-type":"ROR","asserted-by":"publisher"}],"name":"Heart and Vascular Center, Semmelweis University 2 , Budapest,","place":["Hungary"]},{"name":"Hungarian Marfan Foundation 3 , Budapest,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5553-6553","authenticated-orcid":true,"given":"Mikl\u00f3s","family":"Kellermayer","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01g9ty582","id-type":"ROR","asserted-by":"publisher"}],"name":"Semmelweis University 1 Department of Biophysics and Radiation Biology, , Budapest,","place":["Hungary"]},{"name":"HUN-REN-SU Biophysical Virology Research Group 5 , Budapest,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2347-5928","authenticated-orcid":true,"given":"Bal\u00e1zs","family":"Kiss","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01g9ty582","id-type":"ROR","asserted-by":"publisher"}],"name":"Semmelweis University 1 Department of Biophysics and Radiation Biology, , Budapest,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2025,3,10]]},"reference":[{"key":"2025042818005143800_bib1","doi-asserted-by":"publisher","first-page":"16756","DOI":"10.1038\/s41598-020-73802-w","article-title":"Effects of fibrillin mutations on the behavior of heart muscle cells in Marfan syndrome","volume":"10","author":"Aalders","year":"2020","journal-title":"Sci. Rep."},{"key":"2025042818005143800_bib2","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1186\/s13023-020-01369-w","article-title":"Increased visceral arterial tortuosity in Marfan syndrome","volume":"15","author":"\u00c1gg","year":"2020","journal-title":"Orphanet J. Rare Dis."},{"key":"2025042818005143800_bib3","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1093\/eurjhf\/hfq127","article-title":"Evidence for Marfan cardiomyopathy","volume":"12","author":"Alpendurada","year":"2010","journal-title":"Eur. J. Heart Fail."},{"key":"2025042818005143800_bib4","doi-asserted-by":"publisher","first-page":"227","DOI":"10.5603\/CJ.2013.0066","article-title":"The role of transforming growth factor-beta in Marfan syndrome","volume":"20","author":"Benke","year":"2013","journal-title":"Cardiol. J."},{"key":"2025042818005143800_bib5","doi-asserted-by":"publisher","first-page":"jcs258684","DOI":"10.1242\/jcs.258684","article-title":"Titin M-line insertion sequence 7 is required for proper cardiac function in mice","volume":"134","author":"Biquand","year":"2021","journal-title":"J. Cell Sci."},{"key":"2025042818005143800_bib6","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1038\/pr.2015.110","article-title":"Intrinsic cardiomyopathy in Marfan syndrome: Results from in-vivo and ex-vivo studies of the Fbn1C1039G\/+ model and longitudinal findings in humans","volume":"78","author":"Campens","year":"2015","journal-title":"Pediatr. Res."},{"key":"2025042818005143800_bib7","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1161\/01.RES.86.1.59","article-title":"Differential expression of cardiac titin isoforms and modulation of cellular stiffness","volume":"86","author":"Cazorla","year":"2000","journal-title":"Circ. Res."},{"key":"2025042818005143800_bib8","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.mayocp.2013.08.022","article-title":"Epidemiological profile of Marfan syndrome in a general population: A national database study","volume":"89","author":"Chiu","year":"2014","journal-title":"Mayo Clin. Proc."},{"key":"2025042818005143800_bib9","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1172\/JCI71059","article-title":"Abnormal muscle mechanosignaling triggers cardiomyopathy in mice with Marfan syndrome","volume":"124","author":"Cook","year":"2014","journal-title":"J. Clin. Invest."},{"key":"2025042818005143800_bib10","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.70024","article-title":"Assessment of myocardial fibrosis in marfan syndrome using cardiac magnetic resonance imaging","volume":"12","author":"Demolder","year":"2024","journal-title":"Mol. Genet. Genomic Med."},{"key":"2025042818005143800_bib11","doi-asserted-by":"publisher","first-page":"751","DOI":"10.3390\/diagnostics10100751","article-title":"Myocardial function, heart failure and arrhythmia in Marfan syndrome: A systematic literature review","volume":"10","author":"Demolder","year":"2020","journal-title":"Diagnostics (Basel)"},{"key":"2025042818005143800_bib12","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1161\/01.RES.86.11.1114","article-title":"Series of exon-skipping events in the elastic spring region of titin as the structural basis for myofibrillar elastic diversity","volume":"86","author":"Freiburg","year":"2000","journal-title":"Circ. Res."},{"key":"2025042818005143800_bib13","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1016\/j.oret.2023.02.014","article-title":"Retinal arterial tortuosity in Marfan and loeys-dietz syndromes","volume":"7","author":"Ghoraba","year":"2023","journal-title":"Ophthalmol. Retina"},{"key":"2025042818005143800_bib14","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1038\/s41594-023-00950-8","article-title":"Fibrillin microfibril structure identifies long-range effects of inherited pathogenic mutations affecting a key regulatory latent TGF\u03b2-binding site","volume":"30","author":"Godwin","year":"2023","journal-title":"Nat. Struct. Mol. Biol."},{"key":"2025042818005143800_bib15","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1016\/S0006-3495(95)80278-X","article-title":"Passive tension in cardiac muscle: Contribution of collagen, titin, microtubules, and intermediate filaments","volume":"68","author":"Granzier","year":"1995","journal-title":"Biophys. J."},{"key":"2025042818005143800_bib16","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1161\/01.RES.0000117769.88862.F8","article-title":"The giant protein titin: A major player in myocardial mechanics, signaling, and disease","volume":"94","author":"Granzier","year":"2004","journal-title":"Circ. Res."},{"key":"2025042818005143800_bib17","doi-asserted-by":"publisher","first-page":"30","DOI":"10.14503\/THIJ-13-3848","article-title":"Echocardiographic versus histologic findings in Marfan syndrome","volume":"42","author":"Gu","year":"2015","journal-title":"Tex. Heart Inst. J."},{"key":"2025042818005143800_bib18","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1056\/NEJMoa1110186","article-title":"Truncations of titin causing dilated cardiomyopathy","volume":"366","author":"Herman","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"2025042818005143800_bib19","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1038\/nrcardio.2013.105","article-title":"Dilated cardiomyopathy: The complexity of a diverse genetic architecture","volume":"10","author":"Hershberger","year":"2013","journal-title":"Nat. Rev. Cardiol."},{"key":"2025042818005143800_bib20","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1136\/hrt.2010.212100","article-title":"The translational science of Marfan syndrome","volume":"97","author":"Jondeau","year":"2011","journal-title":"Heart"},{"key":"2025042818005143800_bib21","doi-asserted-by":"publisher","first-page":"1965","DOI":"10.1016\/S0140-6736(05)67789-6","article-title":"Marfan\u2019s syndrome","volume":"366","author":"Judge","year":"2005","journal-title":"Lancet"},{"key":"2025042818005143800_bib22","doi-asserted-by":"publisher","first-page":"2279","DOI":"10.1016\/j.jacc.2018.07.095","article-title":"Diffuse myocardial fibrosis in children and adolescents with Marfan syndrome and loeys-dietz syndrome","volume":"72","author":"Karur","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"2025042818005143800_bib23","doi-asserted-by":"publisher","first-page":"11110","DOI":"10.3390\/ijms222011110","article-title":"Increased expression of N2BA titin corresponds to more compliant myofibrils in athlete\u2019s heart","volume":"22","author":"Kellermayer","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"2025042818005143800_bib24","doi-asserted-by":"publisher","DOI":"10.1172\/JCI169753","article-title":"Truncated titin is structurally integrated into the human dilated cardiomyopathic sarcomere","volume":"134","author":"Kellermayer","year":"2024","journal-title":"J. Clin. Invest."},{"key":"2025042818005143800_bib25","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1161\/01.RES.80.2.290","article-title":"The giant protein titin. Emerging roles in physiology and pathophysiology","volume":"80","author":"Labeit","year":"1997","journal-title":"Circ. Res."},{"key":"2025042818005143800_bib26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.echo.2014.10.003","article-title":"Recommendations for cardiac chamber quantification by echocardiography in adults: An update from the American society of Echocardiography and the European association of cardiovascular imaging","volume":"28","author":"Lang","year":"2015","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"2025042818005143800_bib27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.cca.2006.06.035","article-title":"Cardiac titin: Structure, functions and role in disease","volume":"375","author":"LeWinter","year":"2007","journal-title":"Clin. Chim. Acta"},{"key":"2025042818005143800_bib28","doi-asserted-by":"publisher","first-page":"1302285","DOI":"10.3389\/fcell.2023.1302285","article-title":"The extracellular matrix glycoprotein fibrillin-1 in health and disease","volume":"11","author":"Li","year":"2024","journal-title":"Front. Cell Dev. Biol."},{"key":"2025042818005143800_bib29","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1016\/j.cardiores.2007.03.029","article-title":"Sense and stretchability: The role of titin and titin-associated proteins in myocardial stress-sensing and mechanical dysfunction","volume":"77","author":"Linke","year":"2008","journal-title":"Cardiovasc. Res."},{"key":"2025042818005143800_bib30","doi-asserted-by":"publisher","first-page":"2903","DOI":"10.1093\/cvr\/cvab328","article-title":"Titin (TTN): From molecule to modifications, mechanics, and medical significance","volume":"118","author":"Loescher","year":"2022","journal-title":"Cardiovasc. Res."},{"key":"2025042818005143800_bib31","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1136\/jmg.2009.072785","article-title":"The revised Ghent nosology for the Marfan syndrome","volume":"47","author":"Loeys","year":"2010","journal-title":"J. Med. Genet."},{"key":"2025042818005143800_bib32","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1161\/01.RES.0000143901.37063.2f","article-title":"Passive stiffness changes caused by upregulation of compliant titin isoforms in human dilated cardiomyopathy hearts","volume":"95","author":"Makarenko","year":"2004","journal-title":"Circ. Res."},{"key":"2025042818005143800_bib33","doi-asserted-by":"publisher","first-page":"e150","DOI":"10.1161\/01.CIR.0000155243.70456.F4","article-title":"Treatment of aortic disease in patients with Marfan syndrome","volume":"111","author":"Milewicz","year":"2005","journal-title":"Circulation"},{"key":"2025042818005143800_bib34","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1006\/jmcc.1994.1045","article-title":"Titin, myosin light chains and C-protein in the developing and failing human heart","volume":"26","author":"Morano","year":"1994","journal-title":"J. Mol. Cell. Cardiol."},{"key":"2025042818005143800_bib35","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1186\/s13023-020-01581-8","article-title":"Myocardial disease and ventricular arrhythmia in Marfan syndrome: A prospective study","volume":"15","author":"Mui\u00f1o-Mosquera","year":"2020","journal-title":"Orphanet J. Rare Dis."},{"key":"2025042818005143800_bib36","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1161\/01.CIR.0000135591.37759.AF","article-title":"Altered titin expression, myocardial stiffness, and left ventricular function in patients with dilated cardiomyopathy","volume":"110","author":"Nagueh","year":"2004","journal-title":"Circulation"},{"key":"2025042818005143800_bib37","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1161\/01.CIR.0000029803.93022.93","article-title":"Titin isoform switch in ischemic human heart disease","volume":"106","author":"Neagoe","year":"2002","journal-title":"Circulation"},{"key":"2025042818005143800_bib38","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1016\/j.amjcard.2010.05.038","article-title":"Frequency and age-related course of mitral valve dysfunction in the Marfan syndrome","volume":"106","author":"Rybczynski","year":"2010","journal-title":"Am. J. Cardiol."},{"key":"2025042818005143800_bib39","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1016\/j.amjcard.2010.08.070","article-title":"Predictors of outcome of mitral valve prolapse in patients with the Marfan syndrome","volume":"107","author":"Rybczynski","year":"2011","journal-title":"Am. J. Cardiol."},{"key":"2025042818005143800_bib40","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.54141","article-title":"Frequency of cardiac valvulopathies in patients with marfan syndrome: A systematic review and meta-analysis","volume":"16","author":"Sama","year":"2024","journal-title":"Cureus"},{"key":"2025042818005143800_bib41","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. Methods"},{"key":"2025042818005143800_bib42","doi-asserted-by":"publisher","first-page":"1916","DOI":"10.3174\/ajnr.A6732","article-title":"Intracranial arterial tortuosity in marfan syndrome and loeys-dietz syndrome: Tortuosity index evaluation is useful in the differential diagnosis","volume":"41","author":"Spinardi","year":"2020","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"2025042818005143800_bib43","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1186\/s13023-020-01569-4","article-title":"Optimising the mutation screening strategy in Marfan syndrome and identifying genotypes with more severe aortic involvement","volume":"15","author":"Stengl","year":"2020","journal-title":"Orphanet J. Rare Dis."},{"key":"2025042818005143800_bib44","doi-asserted-by":"publisher","first-page":"7561","DOI":"10.3390\/ijms24087561","article-title":"Nanoscale structural comparison of fibrillin-1 microfibrils isolated from marfan and non-marfan syndrome human aorta","volume":"24","author":"\u0218ulea","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"2025042818005143800_bib45","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.117.002058","article-title":"Impact of pathogenic FBN1 variant types on the progression of aortic disease in patients with marfan syndrome","volume":"11","author":"Takeda","year":"2018","journal-title":"Circ. Genom. Precis. Med."},{"key":"2025042818005143800_bib46","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1038\/s41467-017-01144-9","article-title":"The giant protein titin regulates the length of the striated muscle thick filament","volume":"8","author":"Tonino","year":"2017","journal-title":"Nat. Commun."},{"key":"2025042818005143800_bib47","doi-asserted-by":"publisher","first-page":"3226","DOI":"10.1016\/S0006-3495(00)76555-6","article-title":"Extensibility of isoforms of cardiac titin: Variation in contour length of molecular subsegments provides a basis for cellular passive stiffness diversity","volume":"79","author":"Trombit\u00e1s","year":"2000","journal-title":"Biophys. J."},{"key":"2025042818005143800_bib48","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1002\/mgg3.489","article-title":"Survival, causes of death, and cardiovascular events in patients with Marfan syndrome","volume":"6","author":"Vanem","year":"2018","journal-title":"Mol. Genet. Genomic Med."},{"key":"2025042818005143800_bib49","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/S0008-6363(03)00328-6","article-title":"Titin isoform expression in normal and hypertensive myocardium","volume":"59","author":"Warren","year":"2003","journal-title":"Cardiovasc. Res."},{"key":"2025042818005143800_bib50","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1016\/j.mod.2004.07.003","article-title":"Titin isoform changes in rat myocardium during development","volume":"121","author":"Warren","year":"2004","journal-title":"Mech. Dev."},{"key":"2025042818005143800_bib51","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1136\/heartjnl-2024-323922","article-title":"Evidence of cardiomyopathy associated with Marfan syndrome in children","volume":"110","author":"Weigand","year":"2024","journal-title":"Heart"},{"key":"2025042818005143800_bib52","doi-asserted-by":"publisher","first-page":"1384","DOI":"10.1161\/01.CIR.0000029804.61510.02","article-title":"Changes in titin isoform expression in pacing-induced cardiac failure give rise to increased passive muscle stiffness","volume":"106","author":"Wu","year":"2002","journal-title":"Circulation"},{"key":"2025042818005143800_bib53","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.mrrev.2015.04.002","article-title":"Engineered mutations in fibrillin-1 leading to Marfan syndrome act at the protein, cellular and organismal levels","volume":"765","author":"Zeyer","year":"2015","journal-title":"Mutat. Res. Rev. Mutat. Res."}],"container-title":["Journal of General Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jgp\/article-pdf\/doi\/10.1085\/jgp.202413690\/1940470\/jgp_202413690.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jgp\/article-pdf\/doi\/10.1085\/jgp.202413690\/1940470\/jgp_202413690.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T18:00:58Z","timestamp":1745863258000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jgp\/article\/157\/3\/e202413690\/277312\/Marfan-syndrome-cardiomyocytes-show-excess-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,10]]},"references-count":53,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,5,5]]}},"URL":"https:\/\/doi.org\/10.1085\/jgp.202413690","relation":{},"ISSN":["0022-1295","1540-7748"],"issn-type":[{"value":"0022-1295","type":"print"},{"value":"1540-7748","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,10]]},"article-number":"e202413690"}}