{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T13:12:08Z","timestamp":1789996328256,"version":"4.0.1"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["17POST33630095"],"award-info":[{"award-number":["17POST33630095"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["19POST34380448"],"award-info":[{"award-number":["19POST34380448"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["23CDA1046498"],"award-info":[{"award-number":["23CDA1046498"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001030","name":"National Heart Foundation of Australia","doi-asserted-by":"publisher","award":["107192"],"award-info":[{"award-number":["107192"]}],"id":[{"id":"10.13039\/501100001030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["Medical Research Future Fund"],"award-info":[{"award-number":["Medical Research Future Fund"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AR079435"],"award-info":[{"award-number":["R01 AR079435"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AR079477"],"award-info":[{"award-number":["R01 AR079477"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AR078001"],"award-info":[{"award-number":["R01 AR078001"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL130356"],"award-info":[{"award-number":["R01 HL130356"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL105826"],"award-info":[{"award-number":["R01 HL105826"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R38 HL155775"],"award-info":[{"award-number":["R38 HL155775"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL143490"],"award-info":[{"award-number":["R01 HL143490"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Basic Res Cardiol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>During heart failure (HF), gene and protein expression profiles undergo extensive compensatory and pathological remodeling. We previously observed that fast skeletal myosin binding protein-C (fMyBP-C) is upregulated in diseased mouse hearts. While fMyBP-C shares significant homology with its cardiac paralog, cardiac myosin binding protein-C (cMyBP-C), there are key differences that may affect cardiac function. However, the consequence of cardiac expression of fMyBP-C is unknown. Here, we aim to elucidate the impact of fMyBP-C expression on cardiac function and pathology. To determine the sufficiency of fMyBP-C to cause cardiac dysfunction, we generated cardiac-specific fMyBP-C over-expression mice. These mice were crossed into cMyBP-C null mice to assess the effect of fMyBP-C in the complete absence of cMyBP-C. Finally, fMyBP-C null mice underwent transverse aortic constriction (TAC) to define the requirement of fMyBP-C in HF. We confirmed the upregulation of fMyBP-C in several models of cardiac disease, including lineage tracing models. Low levels of fMyBP-C caused mild cardiac remodeling and sarcomere dysfunction. Exclusive expression of fMyBP-C in a HF model exacerbated cardiac pathology. Furthermore, reduction of fMyBP-C expression by shRNA in HF improved cardiac function. Following pressure overload, fMyBP-C null mice demonstrated greater resistance to cardiac decompensation. Mechanistically, our data suggest the differential regulation of the myosin super-relaxed state by cMyBP-C and fMyBP-C plays a contributing role. These findings suggest the elevated expression of fMyBP-C in diseased hearts is a pathological response. Targeted therapies to prevent upregulation of fMyBP-C may prove beneficial in the treatment of HF.<\/jats:p>","DOI":"10.1007\/s00395-026-01202-8","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T10:50:28Z","timestamp":1785927028000},"page":"1047-1061","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fast skeletal myosin binding protein-C expression exacerbates dysfunction in heart failure"],"prefix":"10.1007","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3754-6405","authenticated-orcid":false,"given":"James W.","family":"McNamara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taejeong","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perwez","family":"Alam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akhil","family":"Baby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Binek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalyani","family":"Ananthamohan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohit R.","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle L.","family":"Nieman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marloes","family":"van den Berg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brent M.","family":"Cernyar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheryl E.","family":"Koch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malina J.","family":"Ivey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"IV","given":"Thomas L.","family":"Lynch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James T.","family":"Pearson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Rubinstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.-P.","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John N.","family":"Lorenz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer E.","family":"Van Eyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onur","family":"Kanisicak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakthivel","family":"Sadayappan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"1202_CR1","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1038\/s41569-025-01165-8","volume":"22","author":"I Andreadou","year":"2025","unstructured":"Andreadou I, Ghigo A, Nikolaou P-E, Swirski FK, Thackeray JT, Heusch G, Vilahur G (2025) Immunometabolism in heart failure. Nat Rev Cardiol 22:751\u2013772. https:\/\/doi.org\/10.1038\/s41569-025-01165-8","journal-title":"Nat Rev Cardiol"},{"key":"1202_CR2","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1016\/j.yjmcc.2009.11.014","volume":"48","author":"D Barefield","year":"2010","unstructured":"Barefield D, Sadayappan S (2010) Phosphorylation and function of cardiac myosin binding protein-C in health and disease. J Mol Cell Cardiol 48:866\u2013875. https:\/\/doi.org\/10.1016\/j.yjmcc.2009.11.014","journal-title":"J Mol Cell Cardiol"},{"key":"1202_CR3","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/j.yjmcc.2019.03.006","volume":"129","author":"DY Barefield","year":"2019","unstructured":"Barefield DY, McNamara JW, Lynch TL, Kuster DWD, Govindan S, Haar L, Wang Y, Taylor EN, Lorenz JN, Nieman ML, Zhu G, Luther PK, Varr\u00f3 A, Dobrev D, Ai X, Janssen PML, Kass DA, Jones WK, Gilbert RJ, Sadayappan S (2019) Ablation of the calpain-targeted site in cardiac myosin binding protein-C is cardioprotective during ischemia-reperfusion injury. J Mol Cell Cardiol 129:236\u2013246. https:\/\/doi.org\/10.1016\/j.yjmcc.2019.03.006","journal-title":"J Mol Cell Cardiol"},{"key":"1202_CR4","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.01442","author":"E Farrell","year":"2018","unstructured":"Farrell E, Armstrong AE, Grimes AC, Naya FJ, de Lange WJ, Ralphe JC (2018) Transcriptome analysis of cardiac hypertrophic growth in MYBPC3-null mice suggests early responders in hypertrophic remodeling. Front Physiol. https:\/\/doi.org\/10.3389\/fphys.2018.01442","journal-title":"Front Physiol"},{"key":"1202_CR5","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.1093\/eurheartj\/ehab068","volume":"42","author":"GA Figtree","year":"2021","unstructured":"Figtree GA, Broadfoot K, Casadei B, Califf R, Crea F, Drummond GR, Freedman JE, Guzik TJ, Harrison D, Hausenloy DJ, Hill JA, Januzzi JL, Kingwell BA, Lam CSP, MacRae CA, Misselwitz F, Miura T, Ritchie RH, Tomaszewski M, Wu JC, Xiao J, Zannad F (2021) A call to action for new global approaches to cardiovascular disease drug solutions. Eur Heart J 42:1464\u20131475. https:\/\/doi.org\/10.1093\/eurheartj\/ehab068","journal-title":"Eur Heart J"},{"key":"1202_CR6","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1161\/01.res.82.1.130","volume":"82","author":"F Fougerousse","year":"1998","unstructured":"Fougerousse F, Delezoide AL, Fiszman MY, Schwartz K, Beckmann JS, Carrier L (1998) Cardiac myosin binding protein C gene is specifically expressed in heart during murine and human development. Circ Res 82:130\u2013133. https:\/\/doi.org\/10.1161\/01.res.82.1.130","journal-title":"Circ Res"},{"key":"1202_CR7","doi-asserted-by":"publisher","first-page":"2127","DOI":"10.1172\/jci98215","volume":"128","author":"X Fu","year":"2018","unstructured":"Fu X, Khalil H, Kanisicak O, Boyer JG, Vagnozzi RJ, Maliken BD, Sargent MA, Prasad V, Valiente-Alandi I, Blaxall BC, Molkentin JD (2018) Specialized fibroblast differentiated states underlie scar formation in the infarcted mouse heart. J Clin Invest 128:2127\u20132143. https:\/\/doi.org\/10.1172\/jci98215","journal-title":"J Clin Invest"},{"key":"1202_CR8","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1161\/01.res.82.1.124","volume":"82","author":"M Gautel","year":"1998","unstructured":"Gautel M, F\u00fcrst DO, Cocco A, Schiaffino S (1998) Isoform transitions of the myosin binding protein C family in developing human and mouse muscles: lack of isoform transcomplementation in cardiac muscle. Circ Res 82:124\u2013129. https:\/\/doi.org\/10.1161\/01.res.82.1.124","journal-title":"Circ Res"},{"key":"1202_CR9","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1093\/cvr\/cvm079","volume":"77","author":"N Hamdani","year":"2007","unstructured":"Hamdani N, Kooij V, van Dijk S, Merkus D, Paulus WJ, Remedios C, Duncker DJ, Stienen GJM, van der Velden J (2007) Sarcomeric dysfunction in heart failure. Cardiovasc Res 77:649\u2013658. https:\/\/doi.org\/10.1093\/cvr\/cvm079","journal-title":"Cardiovasc Res"},{"key":"1202_CR10","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1172\/JCI15380","volume":"109","author":"M Hoshijima","year":"2002","unstructured":"Hoshijima M, Chien KR (2002) Mixed signals in heart failure: cancer rules. J Clin Invest 109:849\u2013855. https:\/\/doi.org\/10.1172\/JCI15380","journal-title":"J Clin Invest"},{"key":"1202_CR11","doi-asserted-by":"publisher","first-page":"18763","DOI":"10.1073\/pnas.1413922112","volume":"111","author":"T Kampourakis","year":"2014","unstructured":"Kampourakis T, Yan Z, Gautel M, Sun YB, Irving M (2014) Myosin binding protein-C activates thin filaments and inhibits thick filaments in heart muscle cells. Proc Natl Acad Sci U S A 111:18763\u201318768. https:\/\/doi.org\/10.1073\/pnas.1413922112","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1202_CR12","first-page":"p 87","volume-title":"Cardiovascular proteomics: methods and protocols","author":"LA Kane","year":"2007","unstructured":"Kane LA, Neverova I, Van Eyk JE (2007) Subfractionation of heart tissue. In: Vivanco F (ed) Cardiovascular proteomics: methods and protocols. Humana Press, Totowa, NJ, p p 87-90"},{"key":"1202_CR13","doi-asserted-by":"publisher","first-page":"E1355","DOI":"10.1073\/pnas.1614020114","volume":"114","author":"RW Kensler","year":"2017","unstructured":"Kensler RW, Craig R, Moss RL (2017) Phosphorylation of cardiac myosin binding protein C releases myosin heads from the surface of cardiac thick filaments. Proc Natl Acad Sci U S A 114:E1355-e1364. https:\/\/doi.org\/10.1073\/pnas.1614020114","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1202_CR14","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1161\/01.Res.0000096363.85588.9a","volume":"93","author":"FS Korte","year":"2003","unstructured":"Korte FS, McDonald KS, Harris SP, Moss RL (2003) Loaded shortening, power output, and rate of force redevelopment are increased with knockout of cardiac myosin binding protein-C. Circ Res 93:752\u2013758. https:\/\/doi.org\/10.1161\/01.Res.0000096363.85588.9a","journal-title":"Circ Res"},{"key":"1202_CR15","doi-asserted-by":"publisher","first-page":"21882","DOI":"10.1073\/pnas.1910549116","volume":"116","author":"A Li","year":"2019","unstructured":"Li A, Nelson SR, Rahmanseresht S, Braet F, Cornachione AS, Previs SB, O\u2019Leary TS, McNamara JW, Rassier DE, Sadayappan S, Previs MJ, Warshaw DM (2019) Skeletal MyBP-C isoforms tune the molecular contractility of divergent skeletal muscle systems. Proc Natl Acad Sci USA 116:21882\u201321892. https:\/\/doi.org\/10.1073\/pnas.1910549116","journal-title":"Proc Natl Acad Sci USA"},{"key":"1202_CR16","doi-asserted-by":"publisher","first-page":"2843","DOI":"10.1038\/s41467-020-16584-z","volume":"11","author":"M Li","year":"2020","unstructured":"Li M, Parker BL, Pearson E, Hunter B, Cao J, Koay YC, Guneratne O, James DE, Yang J, Lal S, O\u2019Sullivan JF (2020) Core functional nodes and sex-specific pathways in human ischaemic and dilated cardiomyopathy. Nat Commun 11:2843. https:\/\/doi.org\/10.1038\/s41467-020-16584-z","journal-title":"Nat Commun"},{"key":"1202_CR17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0069671","volume":"8","author":"B Lin","year":"2013","unstructured":"Lin B, Govindan S, Lee K, Zhao P, Han R, Runte KE, Craig R, Palmer BM, Sadayappan S (2013) Cardiac myosin binding protein-C plays no regulatory role in skeletal muscle structure and function. PLoS ONE 8:e69671. https:\/\/doi.org\/10.1371\/journal.pone.0069671","journal-title":"PLoS ONE"},{"key":"1202_CR18","doi-asserted-by":"publisher","first-page":"2604","DOI":"10.1038\/s41598-018-21053-1","volume":"8","author":"BL Lin","year":"2018","unstructured":"Lin BL, Li A, Mun JY, Previs MJ, Previs SB, Campbell SG, Dos Remedios CG, Tombe PP, Craig R, Warshaw DM, Sadayappan S (2018) Skeletal myosin binding protein-C isoforms regulate thin filament activity in a Ca(2+)-dependent manner. Sci Rep 8:2604. https:\/\/doi.org\/10.1038\/s41598-018-21053-1","journal-title":"Sci Rep"},{"key":"1202_CR19","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1161\/CIRCRESAHA.122.321461","volume":"131","author":"P Lu","year":"2022","unstructured":"Lu P, Wu B, Feng X, Cheng W, Kitsis RN, Zhou B (2022) Cardiac myosin heavy chain reporter mice to study heart development and disease. Circ Res 131:364\u2013366. https:\/\/doi.org\/10.1161\/CIRCRESAHA.122.321461","journal-title":"Circ Res"},{"key":"1202_CR20","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.yjmcc.2021.03.009","volume":"156","author":"TLt Lynch","year":"2021","unstructured":"Lynch TLt, Kumar M, McNamara JW, Kuster DWD, Sivaguru M, Singh RR, Previs MJ, Lee KH, Kuffel G, Zilliox MJ, Lin BL, Ma W, Gibson AM, Blaxall BC, Nieman ML, Lorenz JN, Leichter DM, Leary OP, Janssen PML, de Tombe PP, Gilbert RJ, Craig R, Irving T, Warshaw DM, Sadayappan S (2021) Amino terminus of cardiac myosin binding protein-C regulates cardiac contractility. J Mol Cell Cardiol 156:33\u201344. https:\/\/doi.org\/10.1016\/j.yjmcc.2021.03.009","journal-title":"J Mol Cell Cardiol"},{"key":"1202_CR21","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004332","volume":"11","author":"X Ma","year":"2015","unstructured":"Ma X, Gao L, Karamanlidis G, Gao P, Lee CF, Garcia-Menendez L, Tian R, Tan K (2015) Revealing pathway dynamics in heart diseases by analyzing multiple differential networks. PLoS Comput Biol 11:e1004332. https:\/\/doi.org\/10.1371\/journal.pcbi.1004332","journal-title":"PLoS Comput Biol"},{"key":"1202_CR22","doi-asserted-by":"publisher","first-page":"2089","DOI":"10.1161\/CIRCULATIONAHA.119.041694","volume":"140","author":"E Martini","year":"2019","unstructured":"Martini E, Kunderfranco P, Peano C, Carullo P, Cremonesi M, Schorn T, Carriero R, Termanini A, Colombo FS, Jachetti E, Panico C, Faggian G, Fumero A, Torracca L, Molgora M, Cibella J, Pagiatakis C, Brummelman J, Alvisi G, Mazza EMC, Colombo MP, Lugli E, Condorelli G, Kallikourdis M (2019) Single-cell sequencing of mouse heart immune infiltrate in pressure overload\u2013driven heart failure reveals extent of immune activation. Circulation 140:2089\u20132107. https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.119.041694","journal-title":"Circulation"},{"key":"1202_CR23","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1172\/jci7377","volume":"104","author":"BK McConnell","year":"1999","unstructured":"McConnell BK, Jones KA, Fatkin D, Arroyo LH, Lee RT, Aristizabal O, Turnbull DH, Georgakopoulos D, Kass D, Bond M, Niimura H, Schoen FJ, Conner D, Fischman DA, Seidman CE, Seidman JG (1999) Dilated cardiomyopathy in homozygous myosin-binding protein-C mutant mice. J Clin Invest 104:1235\u20131244. https:\/\/doi.org\/10.1172\/jci7377","journal-title":"J Clin Invest"},{"key":"1202_CR24","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.abb.2018.10.007","volume":"660","author":"JW McNamara","year":"2018","unstructured":"McNamara JW, Sadayappan S (2018) Skeletal myosin binding protein-C: an increasingly important regulator of striated muscle physiology. Arch Biochem Biophys 660:121\u2013128. https:\/\/doi.org\/10.1016\/j.abb.2018.10.007","journal-title":"Arch Biochem Biophys"},{"key":"1202_CR25","doi-asserted-by":"publisher","first-page":"11731","DOI":"10.1073\/pnas.1821660116","volume":"116","author":"JW McNamara","year":"2019","unstructured":"McNamara JW, Singh RR, Sadayappan S (2019) Cardiac myosin binding protein-C phosphorylation regulates the super-relaxed state of myosin. Proc Natl Acad Sci U S A 116:11731\u201311736. https:\/\/doi.org\/10.1073\/pnas.1821660116","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1202_CR26","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.1161\/circulationaha.121.057763","volume":"146","author":"NR Mehdiabadi","year":"2022","unstructured":"Mehdiabadi NR, Boon Sim C, Phipson B, Kalathur RKR, Sun Y, Vivien CJ, Ter Huurne M, Piers AT, Hudson JE, Oshlack A, Weintraub RG, Konstantinov IE, Palpant NJ, Elliott DA, Porrello ER (2022) Defining the fetal gene program at single-cell resolution in pediatric dilated cardiomyopathy. Circulation 146:1105\u20131108. https:\/\/doi.org\/10.1161\/circulationaha.121.057763","journal-title":"Circulation"},{"key":"1202_CR27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ejim.2022.04.020","volume":"102","author":"C Morelli","year":"2022","unstructured":"Morelli C, Ingrasciotta G, Jacoby D, Masri A, Olivotto I (2022) Sarcomere protein modulation: the new frontier in cardiovascular medicine and beyond. Eur J Intern Med 102:1\u20137. https:\/\/doi.org\/10.1016\/j.ejim.2022.04.020","journal-title":"Eur J Intern Med"},{"key":"1202_CR28","doi-asserted-by":"publisher","DOI":"10.1113\/jp287759","author":"JT Pearson","year":"2025","unstructured":"Pearson JT, Waddingham MT, Tsuchimochi H, Sonobe T, Tokuhara N, Hirose K, Nayeem MJ, Fujihara Y, Aoyama K, Maack C, Sequeira V (2025) Myosin motor dynamics and cardiac function: insights from in vivo small-angle X-ray scattering and pressure-volume analysis. J Physiol. https:\/\/doi.org\/10.1113\/jp287759","journal-title":"J Physiol"},{"key":"1202_CR29","doi-asserted-by":"publisher","first-page":"15485","DOI":"10.1073\/pnas.1903033116","volume":"116","author":"S Ponnam","year":"2019","unstructured":"Ponnam S, Sevrieva I, Sun YB, Irving M, Kampourakis T (2019) Site-specific phosphorylation of myosin binding protein-C coordinates thin and thick filament activation in cardiac muscle. Proc Natl Acad Sci U S A 116:15485\u201315494. https:\/\/doi.org\/10.1073\/pnas.1903033116","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1202_CR30","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1126\/science.1223602","volume":"337","author":"MJ Previs","year":"2012","unstructured":"Previs MJ, Beck Previs S, Gulick J, Robbins J, Warshaw DM (2012) Molecular mechanics of cardiac myosin-binding protein C in native thick filaments. Science 337:1215\u20131218. https:\/\/doi.org\/10.1126\/science.1223602","journal-title":"Science"},{"key":"1202_CR31","doi-asserted-by":"publisher","DOI":"10.1161\/circheartfailure.121.009521","volume":"15","author":"MJ Previs","year":"2022","unstructured":"Previs MJ, O\u2019Leary TS, Morley MP, Palmer BM, LeWinter M, Yob JM, Pagani FD, Petucci C, Kim MS, Margulies KB, Arany Z, Kelly DP, Day SM (2022) Defects in the proteome and metabolome in human hypertrophic cardiomyopathy. Circ Heart Fail 15:e009521. https:\/\/doi.org\/10.1161\/circheartfailure.121.009521","journal-title":"Circ Heart Fail"},{"key":"1202_CR32","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.202012726","author":"S Rahmanseresht","year":"2021","unstructured":"Rahmanseresht S, Lee KH, O\u2019Leary TS, McNamara JW, Sadayappan S, Robbins J, Warshaw DM, Craig R, Previs MJ (2021) The N terminus of myosin-binding protein C extends toward actin filaments in intact cardiac muscle. J Gen Physiol. https:\/\/doi.org\/10.1085\/jgp.202012726"},{"key":"1202_CR33","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1007\/s10741-007-9034-1","volume":"12","author":"M Rajabi","year":"2007","unstructured":"Rajabi M, Kassiotis C, Razeghi P, Taegtmeyer H (2007) Return to the fetal gene program protects the stressed heart: a strong hypothesis. Heart Fail Rev 12:331\u2013343. https:\/\/doi.org\/10.1007\/s10741-007-9034-1","journal-title":"Heart Fail Rev"},{"key":"1202_CR34","doi-asserted-by":"publisher","first-page":"12650","DOI":"10.1074\/jbc.M110.156646","volume":"286","author":"J Ratti","year":"2011","unstructured":"Ratti J, Rostkova E, Gautel M, Pfuhl M (2011) Structure and interactions of myosin-binding protein C domain C0: cardiac-specific regulation of myosin at its neck? J Biol Chem 286:12650\u201312658. https:\/\/doi.org\/10.1074\/jbc.M110.156646","journal-title":"J Biol Chem"},{"key":"1202_CR35","doi-asserted-by":"publisher","DOI":"10.1126\/science.abo1984","volume":"377","author":"D Reichart","year":"2022","unstructured":"Reichart D, Lindberg EL, Maatz H, Miranda AMA, Viveiros A, Shvetsov N, G\u00e4rtner A, Nadelmann ER, Lee M, Kanemaru K, Ruiz-Orera J, Strohmenger V, DeLaughter DM, Patone G, Zhang H, Woehler A, Lippert C, Kim Y, Adami E, Gorham JM, Barnett SN, Brown K, Buchan RJ, Chowdhury RA, Constantinou C, Cranley J, Felkin LE, Fox H, Ghauri A, Gummert J, Kanda M, Li R, Mach L, McDonough B, Samari S, Shahriaran F, Yapp C, Stanasiuk C, Theotokis PI, Theis FJ, van den Bogaerdt A, Wakimoto H, Ware JS, Worth CL, Barton PJR, Lee YA, Teichmann SA, Milting H, Noseda M, Oudit GY, Heinig M, Seidman JG, Hubner N, Seidman CE (2022) Pathogenic variants damage cell composition and single cell transcription in cardiomyopathies. Science 377:eabo1984. https:\/\/doi.org\/10.1126\/science.abo1984","journal-title":"Science"},{"key":"1202_CR36","doi-asserted-by":"publisher","first-page":"1604","DOI":"10.1016\/j.str.2018.08.007","volume":"26","author":"C Risi","year":"2018","unstructured":"Risi C, Belknap B, Forgacs-Lonart E, Harris SP, Schr\u00f6der GF, White HD, Galkin VE (2018) N-terminal domains of cardiac myosin binding protein C cooperatively activate the thin filament. Structure 26:1604-1611.e1604. https:\/\/doi.org\/10.1016\/j.str.2018.08.007","journal-title":"Structure"},{"key":"1202_CR37","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1161\/circheartfailure.114.001550","volume":"8","author":"PC Rosas","year":"2015","unstructured":"Rosas PC, Liu Y, Abdalla MI, Thomas CM, Kidwell DT, Dusio GF, Mukhopadhyay D, Kumar R, Baker KM, Mitchell BM, Powers PA, Fitzsimons DP, Patel BG, Warren CM, Solaro RJ, Moss RL, Tong CW (2015) Phosphorylation of cardiac myosin-binding protein-C is a critical mediator of diastolic function. Circ Heart Fail 8:582\u2013594. https:\/\/doi.org\/10.1161\/circheartfailure.114.001550","journal-title":"Circ Heart Fail"},{"key":"1202_CR38","doi-asserted-by":"publisher","first-page":"1156","DOI":"10.1161\/01.RES.0000190605.79013.4d","volume":"97","author":"S Sadayappan","year":"2005","unstructured":"Sadayappan S, Gulick J, Osinska H, Martin LA, Hahn HS, Dorn GW 2nd, Klevitsky R, Seidman CE, Seidman JG, Robbins J (2005) Cardiac myosin-binding protein-C phosphorylation and cardiac function. Circ Res 97:1156\u20131163. https:\/\/doi.org\/10.1161\/01.RES.0000190605.79013.4d","journal-title":"Circ Res"},{"key":"1202_CR39","doi-asserted-by":"publisher","first-page":"7","DOI":"10.15420\/cfr.2016:25:2","volume":"3","author":"G Savarese","year":"2017","unstructured":"Savarese G, Lund LH (2017) Global public health burden of heart failure. Card Fail Rev 3:7\u201311. https:\/\/doi.org\/10.15420\/cfr.2016:25:2","journal-title":"Card Fail Rev"},{"key":"1202_CR40","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2003596118","author":"T Song","year":"2021","unstructured":"Song T, McNamara JW, Ma W, Landim-Vieira M, Lee KH, Martin LA, Heiny JA, Lorenz JN, Craig R, Pinto JR, Irving T, Sadayappan S (2021) Fast skeletal myosin-binding protein-C regulates fast skeletal muscle contraction. Proc Natl Acad Sci USA. https:\/\/doi.org\/10.1073\/pnas.2003596118","journal-title":"Proc Natl Acad Sci USA"},{"key":"1202_CR41","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1126\/science.1230719","volume":"339","author":"FK Swirski","year":"2013","unstructured":"Swirski FK, Nahrendorf M (2013) Leukocyte behavior in atherosclerosis, myocardial infarction, and heart failure. Science 339:161\u2013166. https:\/\/doi.org\/10.1126\/science.1230719","journal-title":"Science"},{"key":"1202_CR42","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1111\/j.1749-6632.2009.05100.x","volume":"1188","author":"H Taegtmeyer","year":"2010","unstructured":"Taegtmeyer H, Sen S, Vela D (2010) Return to the fetal gene program: a suggested metabolic link to gene expression in the heart. Ann N Y Acad Sci 1188:191\u2013198. https:\/\/doi.org\/10.1111\/j.1749-6632.2009.05100.x","journal-title":"Ann N Y Acad Sci"},{"key":"1202_CR43","doi-asserted-by":"publisher","first-page":"1401","DOI":"10.1007\/s00204-015-1477-x","volume":"89","author":"YK Tham","year":"2015","unstructured":"Tham YK, Bernardo BC, Ooi JYY, Weeks KL, McMullen JR (2015) Pathophysiology of cardiac hypertrophy and heart failure: signaling pathways and novel therapeutic targets. Arch Toxicol 89:1401\u20131438. https:\/\/doi.org\/10.1007\/s00204-015-1477-x","journal-title":"Arch Toxicol"},{"key":"1202_CR44","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1161\/circresaha.115.306565","volume":"118","author":"JG Travers","year":"2016","unstructured":"Travers JG, Kamal FA, Robbins J, Yutzey KE, Blaxall BC (2016) Cardiac fibrosis: the fibroblast awakens. Circ Res 118:1021\u20131040. https:\/\/doi.org\/10.1161\/circresaha.115.306565","journal-title":"Circ Res"},{"key":"1202_CR45","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.94493","author":"S Vakrou","year":"2018","unstructured":"Vakrou S, Fukunaga R, Foster DB, Sorensen L, Liu Y, Guan Y, Woldemichael K, Pineda-Reyes R, Liu T, Tardiff JC, Leinwand LA, Tocchetti CG, Abraham TP, O\u2019Rourke B, Aon MA, Abraham MR (2018) Allele-specific differences in transcriptome, miRNome, and mitochondrial function in two hypertrophic cardiomyopathy mouse models. JCI Insight. https:\/\/doi.org\/10.1172\/jci.insight.94493","journal-title":"JCI Insight"},{"key":"1202_CR46","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1111\/joim.13094","volume":"288","author":"A van der Pol","year":"2020","unstructured":"van der Pol A, Hoes MF, de Boer RA, van der Meer P (2020) Cardiac foetal reprogramming: a tool to exploit novel treatment targets for the failing heart. J Intern Med 288:491\u2013506. https:\/\/doi.org\/10.1111\/joim.13094","journal-title":"J Intern Med"}],"container-title":["Basic Research in Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00395-026-01202-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00395-026-01202-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00395-026-01202-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:46:17Z","timestamp":1789994777000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00395-026-01202-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,5]]},"references-count":46,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["1202"],"URL":"https:\/\/doi.org\/10.1007\/s00395-026-01202-8","relation":{"references":[{"id-type":"doi","id":"10.1085\/jgp.202012726","asserted-by":"subject"}]},"ISSN":["1435-1803"],"issn-type":[{"value":"1435-1803","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,5]]},"assertion":[{"value":"14 October 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 July 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 July 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 August 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Dr. Sadayappan provided consulting and collaborative research studies to the Leducq Foundation (CURE-PLAN), Red Saree Inc., Alexion, Regel Therapeutics, Affinia Therapeutics Inc., but such work is unrelated to the content of this article.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}