{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:10:35Z","timestamp":1792458635598,"version":"4.5.0"},"reference-count":126,"publisher":"Rockefeller University Press","issue":"6","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["1R01HL171047-01"],"award-info":[{"award-number":["1R01HL171047-01"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["5R35HL144998-05"],"award-info":[{"award-number":["5R35HL144998-05"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["5R01HL128368"],"award-info":[{"award-number":["5R01HL128368"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["P30AR074990"],"award-info":[{"award-number":["P30AR074990"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,11,2]]},"abstract":"<jats:p>Three main contributors to cardiomyocyte diastolic stiffness are (1) passive sarcomere stiffness, (2) microtubules, and (3) diastolic crossbridges (XBs), the XBs that are present in the diastolic phase. However, the relative contributions of these key determinants in heart failure with preserved ejection fraction (HFpEF) conditions are unclear. We quantify the relative contributions of passive sarcomere stress, the microtubule network, and diastolic XB activity to overall diastolic stress in intact cardiomyocytes isolated from two-hit mice, a cardiometabolic HFpEF-like model, in both sexes. The stretch-release protocol was used to obtain the diastolic stress\u2013sarcomere length relation. XB inhibitor and colchicine treatment were used to determine the contributions of diastolic XBs and microtubules, respectively. Passive sarcomere stress was measured in cells treated with both colchicine and the XB inhibitor. Male HFpEF-like cardiomyocytes exhibit increases in both passive sarcomere stress (by 70%) and diastolic XBs (by 52%), whereas female HFpEF-like cardiomyocytes show an increase in passive sarcomere stress alone (by 55%). The microtubule network contributes to diastolic stress by augmenting the extent of diastolic XBs in males. The elevated diastolic XBs in male HFpEF-like mice are accompanied by altered Ca2+ transient, suggesting that remodeled Ca2+ handling accounts, in part, for the enhanced diastolic XB activity in males. These findings imply that, in males, both increased passive sarcomere stiffness and diastolic XB activity represent potential therapeutic targets for reducing cardiomyocyte diastolic stiffness, whereas in females, diastolic stiffness is predominantly driven by elevated passive sarcomere stiffness.<\/jats:p>","DOI":"10.1085\/jgp.202614028","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T06:20:32Z","timestamp":1785910832000},"update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Diastolic contributors in cardiomyocytes of a cardiometabolic HFpEF-like mouse model"],"prefix":"10.1085","volume":"158","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7916-9250","authenticated-orcid":true,"given":"Arooj","family":"Shahid","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02ymw8z06","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Missouri 1 Department of Medical Pharmacology and Physiology, , Columbia, MO,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5261-3229","authenticated-orcid":true,"given":"Timothy S.","family":"McMillen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00cvxb145","id-type":"ROR","asserted-by":"publisher"}],"name":"Center of Translational Muscle Research, Institute for Stem Cell and Regenerative Medicine, University of Washington 2 Department of Anesthesiology and Pain Medicine, , Seattle, WA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0700-765X","authenticated-orcid":true,"given":"Samuel","family":"Daugherty","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02ymw8z06","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Missouri 1 Department of Medical Pharmacology and Physiology, , Columbia, MO,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1847-8325","authenticated-orcid":true,"given":"Anna E.","family":"Burns","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02ymw8z06","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Missouri 1 Department of Medical Pharmacology and Physiology, , Columbia, MO,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0920-6139","authenticated-orcid":true,"given":"Marloes","family":"van den Berg","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03m2x1q45","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Arizona 3 Department of Cellular and Molecular Medicine and Sarver Molecular Cardiovascular Research Program, , Tucson, AZ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5437-9851","authenticated-orcid":true,"given":"Michael","family":"Regnier","sequence":"additional","affiliation":[{"name":"4Department of Bioengineering, University of Washington, Seattle, WA, USA"},{"name":"5Center for Translational Muscle Research, University of Washington, Seattle, WA, USA"},{"name":"6Institute For Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9516-407X","authenticated-orcid":true,"given":"Henk","family":"Granzier","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03m2x1q45","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Arizona 3 Department of Cellular and Molecular Medicine and Sarver Molecular Cardiovascular Research Program, , Tucson, AZ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2509-1936","authenticated-orcid":true,"given":"Mei","family":"Methawasin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02ymw8z06","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Missouri 1 Department of Medical Pharmacology and Physiology, , Columbia, MO,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"2026082509484990100_bib1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abd7064","article-title":"Nicotinamide for the treatment of heart failure with preserved ejection fraction","volume":"13","author":"Abdellatif","year":"2021","journal-title":"Sci. Transl Med."},{"key":"2026082509484990100_bib2","doi-asserted-by":"publisher","first-page":"2306","DOI":"10.1073\/pnas.1516732113","article-title":"Titin strain contributes to the Frank-Starling law of the heart by structural rearrangements of both thin- and thick-filament proteins","volume":"113","author":"Ait-Mou","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026082509484990100_bib3","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1113\/jphysiol.1994.sp020149","article-title":"Mechanism of force inhibition by 2,3-butanedione monoxime in rat cardiac muscle: Roles of [Ca2+]i and cross-bridge kinetics","volume":"476","author":"Backx","year":"1994","journal-title":"J. Physiol."},{"key":"2026082509484990100_bib4","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1016\/j.jacbts.2019.07.008","article-title":"Seipin knockout mice develop heart failure with preserved ejection fraction","volume":"4","author":"Bai","year":"2019","journal-title":"JACC Basic Transl Sci."},{"key":"2026082509484990100_bib5","doi-asserted-by":"publisher","first-page":"2882","DOI":"10.1161\/CIRCULATIONAHA.111.048520","article-title":"Sildenafil and B-type natriuretic peptide acutely phosphorylate titin and improve diastolic distensibility in vivo","volume":"124","author":"Bishu","year":"2011","journal-title":"Circulation"},{"key":"2026082509484990100_bib6","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1161\/01.CIR.0000155257.33485.6D","article-title":"Cardiomyocyte stiffness in diastolic heart failure","volume":"111","author":"Borbely","year":"2005","journal-title":"Circulation"},{"key":"2026082509484990100_bib7","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1038\/s41569-020-0363-2","article-title":"Evaluation and management of heart failure with preserved ejection fraction","volume":"17","author":"Borlaug","year":"2020","journal-title":"Nat. Rev. Cardiol."},{"key":"2026082509484990100_bib8","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1093\/eurheartj\/ehq426","article-title":"Heart failure with preserved ejection fraction: Pathophysiology, diagnosis, and treatment","volume":"32","author":"Borlaug","year":"2011","journal-title":"Eur. Heart J."},{"key":"2026082509484990100_bib9","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1152\/physiol.00057.2014","article-title":"The VCD mouse model of menopause and perimenopause for the study of sex differences in cardiovascular disease and the metabolic syndrome","volume":"31","author":"Brooks","year":"2016","journal-title":"Physiology (Bethesda)"},{"key":"2026082509484990100_bib10","doi-asserted-by":"publisher","first-page":"902","DOI":"10.1161\/CIRCULATIONAHA.119.043930","article-title":"Microtubules increase diastolic stiffness in failing human cardiomyocytes and myocardium","volume":"141","author":"Caporizzo","year":"2020","journal-title":"Circulation"},{"key":"2026082509484990100_bib11","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1038\/s41569-022-00692-y","article-title":"The microtubule cytoskeleton in cardiac mechanics and heart failure","volume":"19","author":"Caporizzo","year":"2022","journal-title":"Nat. Rev. Cardiol."},{"key":"2026082509484990100_bib12","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.1038\/s41591-018-0046-2","article-title":"Suppression of detyrosinated microtubules improves cardiomyocyte function in human heart failure","volume":"24","author":"Chen","year":"2018","journal-title":"Nat. Med."},{"key":"2026082509484990100_bib13","doi-asserted-by":"publisher","first-page":"e14","DOI":"10.1161\/CIRCRESAHA.119.315947","article-title":"Depletion of vasohibin 1 speeds contraction and relaxation in failing human cardiomyocytes","volume":"127","author":"Chen","year":"2020","journal-title":"Circ. Res."},{"key":"2026082509484990100_bib14","doi-asserted-by":"publisher","first-page":"310791","DOI":"10.1155\/2011\/310791","article-title":"Titin-actin interaction: PEVK-actin-based viscosity in a large animal","volume":"2011","author":"Chung","year":"2011","journal-title":"J. Biomed. Biotechnol."},{"key":"2026082509484990100_bib15","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1016\/j.yjmcc.2011.01.005","article-title":"Contribution of titin and extracellular matrix to passive pressure and measurement of sarcomere length in the mouse left ventricle","volume":"50","author":"Chung","year":"2011","journal-title":"J. Mol. Cell Cardiol."},{"key":"2026082509484990100_bib16","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1161\/CIRCULATIONAHA.112.001268","article-title":"Shortening of the elastic tandem immunoglobulin segment of titin leads to diastolic dysfunction","volume":"128","author":"Chung","year":"2013","journal-title":"Circulation"},{"key":"2026082509484990100_bib17","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1016\/j.yjmcc.2011.06.006","article-title":"Titin based viscosity in ventricular physiology: An integrative investigation of PEVK-actin interactions","volume":"51","author":"Chung","year":"2011","journal-title":"J. Mol. Cell Cardiol."},{"key":"2026082509484990100_bib18","doi-asserted-by":"publisher","first-page":"562","DOI":"10.3389\/fphys.2016.00562","article-title":"Myofilament calcium sensitivity: Role in regulation of in vivo cardiac contraction and relaxation","volume":"7","author":"Chung","year":"2016","journal-title":"Front. Physiol."},{"key":"2026082509484990100_bib19","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1016\/0022-2828(90)90123-j","article-title":"Effect of 2,3-butanedione 2-monoxime on slow inward and transient outward currents in rat ventricular myocytes","volume":"22","author":"Coulombe","year":"1990","journal-title":"J. Mol. Cell Cardiol."},{"key":"2026082509484990100_bib20","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1161\/CIRCRESAHA.120.317933","article-title":"Targeting mitochondria-inflammation circuit by beta-hydroxybutyrate mitigates HFpEF","volume":"128","author":"Deng","year":"2021","journal-title":"Circ. Res."},{"key":"2026082509484990100_bib21","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1161\/CIRCHEARTFAILURE.112.968925","article-title":"Myosin cross-bridge dynamics in patients with hypertension and concentric left ventricular remodeling","volume":"5","author":"Donaldson","year":"2012","journal-title":"Circ. Heart Fail"},{"key":"2026082509484990100_bib22","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1038\/nrcardio.2017.65","article-title":"Epidemiology of heart failure with preserved ejection fraction","volume":"14","author":"Dunlay","year":"2017","journal-title":"Nat. Rev. Cardiol."},{"key":"2026082509484990100_bib23","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adm8842","article-title":"Vasohibin inhibition improves myocardial relaxation in a rat model of heart failure with preserved ejection fraction","volume":"16","author":"Eaton","year":"2024","journal-title":"Sci. Transl Med."},{"key":"2026082509484990100_bib24","doi-asserted-by":"publisher","first-page":"H1847","DOI":"10.1152\/ajpheart.01237.2005","article-title":"Impact of osmotic compression on sarcomere structure and myofilament calcium sensitivity of isolated rat myocardium","volume":"291","author":"Farman","year":"2006","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"2026082509484990100_bib25","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.123.032037","article-title":"Common heart failure with preserved ejection fraction animal models yield disparate myofibril mechanics","volume":"13","author":"Fenwick","year":"2024","journal-title":"J. Am. Heart Assoc."},{"key":"2026082509484990100_bib26","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1016\/j.jacc.2020.11.044","article-title":"Etiology-dependent impairment of diastolic cardiomyocyte calcium homeostasis in heart failure with preserved ejection fraction","volume":"77","author":"Frisk","year":"2021","journal-title":"J. Am. Coll. Cardiol."},{"key":"2026082509484990100_bib27","doi-asserted-by":"publisher","first-page":"167295","DOI":"10.1016\/j.jmb.2021.167295","article-title":"Two classes of myosin inhibitors, Para-nitroblebbistatin and Mavacamten, stabilize beta-cardiac myosin in different structural and functional states","volume":"433","author":"Gollapudi","year":"2021","journal-title":"J. Mol. Biol."},{"key":"2026082509484990100_bib28","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":"2026082509484990100_bib29","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1161\/CIRCRESAHA.124.323051","article-title":"Discovery of titin and its role in heart function and disease","volume":"136","author":"Granzier","year":"2025","journal-title":"Circ. Res."},{"key":"2026082509484990100_bib30","doi-asserted-by":"publisher","first-page":"1280","DOI":"10.1161\/01.res.69.5.1280","article-title":"Contractile deactivation and uncoupling of crossbridges. Effects of 2,3-butanedione monoxime on mammalian myocardium","volume":"69","author":"Gwathmey","year":"1991","journal-title":"Circ. Res."},{"key":"2026082509484990100_bib31","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1093\/cvr\/cvs353","article-title":"Deranged myofilament phosphorylation and function in experimental heart failure with preserved ejection fraction","volume":"97","author":"Hamdani","year":"2013","journal-title":"Cardiovasc. Res."},{"key":"2026082509484990100_bib32","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1161\/CIRCHEARTFAILURE.113.000539","article-title":"Myocardial titin hypophosphorylation importantly contributes to heart failure with preserved ejection fraction in a rat metabolic risk model","volume":"6","author":"Hamdani","year":"2013","journal-title":"Circ. Heart Fail"},{"key":"2026082509484990100_bib33","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1007\/s12551-017-0263-9","article-title":"Tampering with springs: Phosphorylation of titin affecting the mechanical function of cardiomyocytes","volume":"9","author":"Hamdani","year":"2017","journal-title":"Biophys. Rev."},{"key":"2026082509484990100_bib34","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1085\/jgp.93.3.411","article-title":"Influence of temperature on the calcium sensitivity of the myofilaments of skinned ventricular muscle from the rabbit","volume":"93","author":"Harrison","year":"1989","journal-title":"J. Gen. Physiol."},{"key":"2026082509484990100_bib35","doi-asserted-by":"publisher","first-page":"C282","DOI":"10.1152\/ajpcell.1990.258.2.C282","article-title":"Modification of temperature dependence of myofilament Ca sensitivity by troponin C replacement","volume":"258","author":"Harrison","year":"1990","journal-title":"Am. J. Physiol."},{"key":"2026082509484990100_bib36","doi-asserted-by":"publisher","first-page":"C274","DOI":"10.1152\/ajpcell.1990.258.2.C274","article-title":"Temperature dependence of myofilament Ca sensitivity of rat, Guinea pig, and frog ventricular muscle","volume":"258","author":"Harrison","year":"1990","journal-title":"Am. J. Physiol."},{"key":"2026082509484990100_bib37","doi-asserted-by":"publisher","first-page":"H348","DOI":"10.1152\/ajpheart.00227.2025","article-title":"Excitation-contraction coupling, cardiomyocyte electrophysiology, and transcriptome profiles in two HFpEF murine models: Etiology and sex-dependent differences","volume":"330","author":"Hegyi","year":"2026","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"2026082509484990100_bib38","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.122.027164","article-title":"Diabetes and excess aldosterone promote heart failure with preserved ejection fraction","volume":"11","author":"Hegyi","year":"2022","journal-title":"J. Am. Heart Assoc."},{"key":"2026082509484990100_bib39","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1161\/01.res.79.3.619","article-title":"Titin develops restoring force in rat cardiac myocytes","volume":"79","author":"Helmes","year":"1996","journal-title":"Circ. Res."},{"key":"2026082509484990100_bib40","doi-asserted-by":"publisher","first-page":"12227","DOI":"10.1021\/bi00163a036","article-title":"Effect of 2,3-butanedione monoxime on myosin and myofibrillar ATPases. An example of an uncompetitive inhibitor","volume":"31","author":"Herrmann","year":"1992","journal-title":"Biochemistry"},{"key":"2026082509484990100_bib41","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.tcm.2012.10.005","article-title":"Tuning the molecular giant titin through phosphorylation: Role in health and disease","volume":"23","author":"Hidalgo","year":"2013","journal-title":"Trends Cardiovasc. Med."},{"key":"2026082509484990100_bib42","doi-asserted-by":"publisher","first-page":"1969","DOI":"10.1016\/j.bpj.2011.02.061","article-title":"A new state of cardiac myosin with very slow ATP turnover: A potential cardioprotective mechanism in the heart","volume":"100","author":"Hooijman","year":"2011","journal-title":"Biophys. J."},{"key":"2026082509484990100_bib43","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1161\/CIRCRESAHA.117.312166","article-title":"Diabetes-induced cardiomyocyte passive stiffening is caused by impaired insulin-dependent titin modification and can Be modulated by Neuregulin-1","volume":"123","author":"Hopf","year":"2018","journal-title":"Circ. Res."},{"key":"2026082509484990100_bib44","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.yjmcc.2024.10.005","article-title":"Cardiomyocyte myofilament function in common animal models of heart failure with preserved ejection fraction","volume":"197","author":"Jani","year":"2024","journal-title":"J. Mol. Cell Cardiol"},{"key":"2026082509484990100_bib45","doi-asserted-by":"publisher","first-page":"pgae039","DOI":"10.1093\/pnasnexus\/pgae039","article-title":"The structural OFF and ON states of myosin can be decoupled from the biochemical super- and disordered-relaxed states","volume":"3","author":"Jani","year":"2024","journal-title":"PNAS Nexus"},{"key":"2026082509484990100_bib46","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.124.038945","article-title":"Myocardial proteome in human heart failure with preserved ejection fraction","volume":"14","author":"Jani","year":"2025","journal-title":"J. Am. Heart Assoc."},{"key":"2026082509484990100_bib47","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.abb.2018.11.011","article-title":"Myocardial relaxation in human heart failure: Why sarcomere kinetics should be center-stage","volume":"661","author":"Janssen","year":"2019","journal-title":"Arch. Biochem. Biophys."},{"key":"2026082509484990100_bib48","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aao0144","article-title":"Histone deacetylase activity governs diastolic dysfunction through a nongenomic mechanism","volume":"10","author":"Jeong","year":"2018","journal-title":"Sci. Transl Med."},{"key":"2026082509484990100_bib49","doi-asserted-by":"publisher","first-page":"8526","DOI":"10.1038\/ncomms9526","article-title":"Detyrosinated microtubules modulate mechanotransduction in heart and skeletal muscle","volume":"6","author":"Kerr","year":"2015","journal-title":"Nat. Commun."},{"key":"2026082509484990100_bib50","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1085\/jgp.201010499","article-title":"Mouse intact cardiac myocyte mechanics: Cross-bridge and titin-based stress in unactivated cells","volume":"137","author":"King","year":"2011","journal-title":"J. Gen. Physiol."},{"key":"2026082509484990100_bib51","doi-asserted-by":"publisher","first-page":"4349170","DOI":"10.1155\/2018\/4349170","article-title":"Optimization of fluorescent labeling for in vivo nanoimaging of sarcomeres in the mouse heart","volume":"2018","author":"Kobirumaki-Shimozawa","year":"2018","journal-title":"Biomed. Res. Int."},{"key":"2026082509484990100_bib52","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1093\/cvr\/cvaa123","article-title":"Empagliflozin improves endothelial and cardiomyocyte function in human heart failure with preserved ejection fraction via reduced pro-inflammatory-oxidative pathways and protein kinase Galpha oxidation","volume":"117","author":"Kolijn","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"2026082509484990100_bib53","doi-asserted-by":"publisher","first-page":"H1461","DOI":"10.1152\/ajpheart.00555.2019","article-title":"Using 4-vinylcyclohexene diepoxide as a model of menopause for cardiovascular disease","volume":"318","author":"Konhilas","year":"2020","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"2026082509484990100_bib54","doi-asserted-by":"publisher","first-page":"120998","DOI":"10.1016\/j.lfs.2022.120998","article-title":"Acetylation and phosphorylation changes to cardiac proteins in experimental HFpEF due to metabolic risk reveal targets for treatment","volume":"309","author":"Koser","year":"2022","journal-title":"Life Sci."},{"key":"2026082509484990100_bib55","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1007\/s12471-016-0814-x","article-title":"Is enhancing cGMP-PKG signalling a promising therapeutic target for heart failure with preserved ejection fraction?","volume":"24","author":"Kovacs","year":"2016","journal-title":"Neth. Heart J."},{"key":"2026082509484990100_bib126","doi-asserted-by":"publisher","first-page":"35557","DOI":"10.1074\/jbc.M405319200","article-title":"Mechanism of blebbistatin inhibition of myosin II","volume":"279","author":"Kov\u00e1cs","year":"2004","journal-title":"J. Biol. Chem"},{"key":"2026082509484990100_bib56","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.1091\/mbc.10.4.1105","article-title":"Detyrosination of tubulin regulates the interaction of intermediate filaments with microtubules in vivo via a kinesin-dependent mechanism","volume":"10","author":"Kreitzer","year":"1999","journal-title":"Mol. Biol. Cell"},{"key":"2026082509484990100_bib57","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.abb.2012.12.004","article-title":"Calcium sensitivity and myofilament lattice structure in titin N2B KO mice","volume":"535","author":"Lee","year":"2013","journal-title":"Arch. Biochem. Biophys."},{"key":"2026082509484990100_bib58","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1016\/j.yjmcc.2010.05.006","article-title":"Calcium sensitivity and the Frank-Starling mechanism of the heart are increased in titin N2B region-deficient mice","volume":"49","author":"Lee","year":"2010","journal-title":"J. Mol. Cell Cardiol."},{"key":"2026082509484990100_bib59","doi-asserted-by":"publisher","first-page":"2137","DOI":"10.1161\/CIRCULATIONAHA.109.860171","article-title":"Cardiac titin: A multifunctional giant","volume":"121","author":"Lewinter","year":"2010","journal-title":"Circulation"},{"key":"2026082509484990100_bib60","doi-asserted-by":"publisher","first-page":"e679","DOI":"10.1161\/CIRCULATIONAHA.116.025995","article-title":"Letter by Lewis and Miller Regarding article, \u201cexperimentally increasing the compliance of titin through RNA binding Motif-20 (RBM20) inhibition improves diastolic function in a mouse model of heart failure with preserved ejection fraction\u201d","volume":"135","author":"Lewis","year":"2017","journal-title":"Circulation"},{"key":"2026082509484990100_bib61","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1038\/nature00938","article-title":"Reverse engineering of the giant muscle protein titin","volume":"418","author":"Li","year":"2002","journal-title":"Nature"},{"key":"2026082509484990100_bib62","doi-asserted-by":"publisher","DOI":"10.1172\/JCI148333","article-title":"HDAC6 modulates myofibril stiffness and diastolic function of the heart","volume":"132","author":"Lin","year":"2022","journal-title":"J. Clin. Invest."},{"key":"2026082509484990100_bib63","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.yjmcc.2021.12.015","article-title":"Mitochondrial protein hyperacetylation underpins heart failure with preserved ejection fraction in mice","volume":"165","author":"Liu","year":"2022","journal-title":"J. Mol. Cell Cardiol."},{"key":"2026082509484990100_bib64","doi-asserted-by":"publisher","first-page":"H869","DOI":"10.1152\/ajpheart.00452.2010","article-title":"Effects of low-level \u03b1-myosin heavy chain expression on contractile kinetics in porcine myocardium","volume":"300","author":"Locher","year":"2011","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"2026082509484990100_bib65","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1038\/s44161-023-00348-1","article-title":"Titin governs myocardial passive stiffness with major support from microtubules and actin and the extracellular matrix","volume":"2","author":"Loescher","year":"2023","journal-title":"Nat. Cardiovasc. Res."},{"key":"2026082509484990100_bib66","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":"2026082509484990100_bib67","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2207615120","article-title":"Structural OFF\/ON transitions of myosin in relaxed porcine myocardium predict calcium-activated force","volume":"120","author":"Ma","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026082509484990100_bib68","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.202213213","article-title":"Cardiac myosin filaments are directly regulated by calcium","volume":"154","author":"Ma","year":"2022","journal-title":"J. Gen. Physiol."},{"key":"2026082509484990100_bib69","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1161\/CIRCGENETICS.114.000957","article-title":"In vivo analysis of troponin C knock-in (A8V) mice: Evidence that TNNC1 is a hypertrophic cardiomyopathy susceptibility gene","volume":"8","author":"Martins","year":"2015","journal-title":"Circ. Cardiovasc. Genet."},{"key":"2026082509484990100_bib70","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/s12551-014-0151-5","article-title":"The role of super-relaxed myosin in skeletal and cardiac muscle","volume":"7","author":"Mcnamara","year":"2015","journal-title":"Biophys. Rev."},{"key":"2026082509484990100_bib71","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0180064","article-title":"MYBPC3 mutations are associated with a reduced super-relaxed state in patients with hypertrophic cardiomyopathy","volume":"12","author":"Mcnamara","year":"2017","journal-title":"PLoS One"},{"key":"2026082509484990100_bib72","doi-asserted-by":"publisher","first-page":"1924","DOI":"10.1161\/CIRCULATIONAHA.113.005610","article-title":"Experimentally increasing titin compliance in a novel mouse model attenuates the Frank-Starling mechanism but has a beneficial effect on diastole","volume":"129","author":"Methawasin","year":"2014","journal-title":"Circulation"},{"key":"2026082509484990100_bib73","doi-asserted-by":"publisher","first-page":"2027","DOI":"10.1093\/cvr\/cvaf171","article-title":"Rbm20 antisense oligonucleotides alleviate diastolic dysfunction in a mouse model of cardiometabolic heart failure (HFpEF)","volume":"121","author":"Methawasin","year":"2025","journal-title":"Cardiovasc. Res."},{"key":"2026082509484990100_bib74","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.119.006609","article-title":"Phosphodiesterase 9a inhibition in mouse models of diastolic dysfunction","volume":"13","author":"Methawasin","year":"2020","journal-title":"Circ. Heart Fail"},{"key":"2026082509484990100_bib75","doi-asserted-by":"publisher","first-page":"H719","DOI":"10.1152\/ajpheart.00575.2024","article-title":"An ovary-intact postmenopausal HFpEF mouse model; menopause is more than just estrogen deficiency","volume":"328","author":"Methawasin","year":"2025","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"2026082509484990100_bib76","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1161\/CIRCULATIONAHA.116.023003","article-title":"Experimentally increasing the compliance of titin through RNA binding Motif-20 (RBM20) inhibition improves diastolic function in a mouse model of heart failure with preserved ejection fraction","volume":"134","author":"Methawasin","year":"2016","journal-title":"Circulation"},{"key":"2026082509484990100_bib77","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1093\/cvr\/cvae070","article-title":"Differential sex-dependent susceptibility to diastolic dysfunction and arrhythmia in cardiomyocytes from obese diabetic heart failure with preserved ejection fraction model","volume":"121","author":"Mira Hernandez","year":"2025","journal-title":"Cardiovasc. Res."},{"key":"2026082509484990100_bib78","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1038\/s41569-020-00480-6","article-title":"Cellular and molecular pathobiology of heart failure with preserved ejection fraction","volume":"18","author":"Mishra","year":"2021","journal-title":"Nat. Rev. Cardiol."},{"key":"2026082509484990100_bib79","doi-asserted-by":"publisher","first-page":"105565","DOI":"10.1016\/j.jbc.2023.105565","article-title":"The biochemically defined super relaxed state of myosin-A paradox","volume":"300","author":"Mohran","year":"2024","journal-title":"J. Biol. Chem."},{"key":"2026082509484990100_bib80","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.63703","article-title":"To lie or not to lie: Super-relaxing with myosins","volume":"10","author":"Nag","year":"2021","journal-title":"Elife"},{"key":"2026082509484990100_bib81","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1093\/cvr\/cvaa228","article-title":"Heart failure with preserved ejection fraction: Insights into diagnosis and pathophysiology","volume":"117","author":"Nagueh","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"2026082509484990100_bib82","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1385\/1-59745-214-9:271","article-title":"Isolation and culture of adult mouse cardiac myocytes","volume":"357","author":"O\u2019Connell","year":"2007","journal-title":"Methods Mol. Biol."},{"key":"2026082509484990100_bib83","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.jacc.2013.02.092","article-title":"A novel paradigm for heart failure with preserved ejection fraction: Comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation","volume":"62","author":"Paulus","year":"2013","journal-title":"J. Am. Coll. Cardiol."},{"key":"2026082509484990100_bib84","doi-asserted-by":"publisher","first-page":"1598","DOI":"10.1161\/CIRCRESAHA.119.313572","article-title":"Heart failure with preserved ejection fraction in perspective","volume":"124","author":"Pfeffer","year":"2019","journal-title":"Circ. Res."},{"key":"2026082509484990100_bib85","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1161\/CIRCRESAHA.124.324387","article-title":"Chronic activation of tubulin tyrosination improves heart function","volume":"135","author":"Pietsch","year":"2024","journal-title":"Circ. Res."},{"key":"2026082509484990100_bib86","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.202413628","article-title":"Spatially resolving how cMyBP-C phosphorylation and haploinsufficiency in porcine and human myofibrils affect beta-cardiac myosin activity","volume":"157","author":"Pilagov","year":"2025","journal-title":"J. Gen. Physiol."},{"key":"2026082509484990100_bib87","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1113\/JP271290","article-title":"Contractile properties of developing human fetal cardiac muscle","volume":"594","author":"Racca","year":"2016","journal-title":"J. Physiol."},{"key":"2026082509484990100_bib88","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abe8952","article-title":"Therapeutic inhibition of RBM20 improves diastolic function in a murine heart failure model and human engineered heart tissue","volume":"13","author":"Radke","year":"2021","journal-title":"Sci. Transl Med."},{"key":"2026082509484990100_bib89","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1016\/j.bpj.2014.07.027","article-title":"PKA phosphorylation of cardiac troponin I modulates activation and relaxation kinetics of ventricular myofibrils","volume":"107","author":"Rao","year":"2014","journal-title":"Biophys. J."},{"key":"2026082509484990100_bib90","doi-asserted-by":"publisher","first-page":"1868","DOI":"10.1056\/NEJMcp1511175","article-title":"Heart failure with preserved ejection fraction","volume":"375","author":"Redfield","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"2026082509484990100_bib91","doi-asserted-by":"publisher","first-page":"aaf0659","DOI":"10.1126\/science.aaf0659","article-title":"Detyrosinated microtubules buckle and bear load in contracting cardiomyocytes","volume":"352","author":"Robison","year":"2016","journal-title":"Science"},{"key":"2026082509484990100_bib92","doi-asserted-by":"publisher","first-page":"3931","DOI":"10.1113\/JP273046","article-title":"Microtubule mechanics in the working myocyte","volume":"595","author":"Robison","year":"2017","journal-title":"J. Physiol."},{"key":"2026082509484990100_bib93","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1161\/CIRCHEARTFAILURE.114.001550","article-title":"Phosphorylation of cardiac Myosin-binding protein-C is a critical mediator of diastolic function","volume":"8","author":"Rosas","year":"2015","journal-title":"Circ. Heart Fail"},{"key":"2026082509484990100_bib94","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.117.004311","article-title":"Relaxation and the role of calcium in isolated contracting myocardium from patients with hypertensive heart disease and heart failure with preserved ejection fraction","volume":"10","author":"Runte","year":"2017","journal-title":"Circ. Heart Fail."},{"key":"2026082509484990100_bib95","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1016\/j.jacc.2019.12.049","article-title":"Menopause-related estrogen decrease and the pathogenesis of HFpEF: JACC review topic of the week","volume":"75","author":"Sabbatini","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"2026082509484990100_bib96","doi-asserted-by":"publisher","first-page":"1684","DOI":"10.1038\/s41467-021-21931-9","article-title":"Xbp1s-FoxO1 axis governs lipid accumulation and contractile performance in heart failure with preserved ejection fraction","volume":"12","author":"Schiattarella","year":"2021","journal-title":"Nat. Commun."},{"key":"2026082509484990100_bib97","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1038\/s41586-019-1100-z","article-title":"Nitrosative stress drives heart failure with preserved ejection fraction","volume":"568","author":"Schiattarella","year":"2019","journal-title":"Nature"},{"key":"2026082509484990100_bib98","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1093\/cvr\/cvaa217","article-title":"Metabolic inflammation in heart failure with preserved ejection fraction","volume":"117","author":"Schiattarella","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"2026082509484990100_bib99","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1007\/s10741-020-09949-5","article-title":"Distinctive patterns of inflammation across the heart failure syndrome","volume":"26","author":"Schiattarella","year":"2021","journal-title":"Heart Fail Rev."},{"key":"2026082509484990100_bib100","doi-asserted-by":"publisher","first-page":"bio057646","DOI":"10.1242\/bio.057646","article-title":"Cardiac myosin super relaxation (SRX): A perspective on fundamental biology, human disease and therapeutics","volume":"10","author":"Schmid","year":"2021","journal-title":"Biol. Open"},{"key":"2026082509484990100_bib101","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.jacc.2010.10.069","article-title":"Tachycardia-induced diastolic dysfunction and resting tone in myocardium from patients with a normal ejection fraction","volume":"58","author":"Selby","year":"2011","journal-title":"J. Am. Coll. Cardiol."},{"key":"2026082509484990100_bib102","doi-asserted-by":"publisher","first-page":"3899","DOI":"10.1113\/JP270354","article-title":"Synergistic role of ADP and Ca(2+) in diastolic myocardial stiffness","volume":"593","author":"Sequeira","year":"2015","journal-title":"J. Physiol."},{"key":"2026082509484990100_bib103","doi-asserted-by":"publisher","first-page":"E7003","DOI":"10.1073\/pnas.1513843112","article-title":"ADP-stimulated contraction: A predictor of thin-filament activation in cardiac disease","volume":"112","author":"Sequeira","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026082509484990100_bib104","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1002\/ehf2.15152","article-title":"Semaglutide normalizes increased cardiomyocyte calcium transients in a rat model of high fat diet-induced obesity","volume":"12","author":"Sequeira","year":"2025","journal-title":"ESC Heart Fail"},{"key":"2026082509484990100_bib105","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1161\/CIRCULATIONAHA.119.041886","article-title":"Research priorities for heart failure with preserved ejection fraction: National heart, lung, and blood Institute working group summary","volume":"141","author":"Shah","year":"2020","journal-title":"Circulation"},{"key":"2026082509484990100_bib106","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1161\/CIRCULATIONAHA.116.021884","article-title":"Phenotype-specific treatment of heart failure with preserved ejection fraction: A multiorgan roadmap","volume":"134","author":"Shah","year":"2016","journal-title":"Circulation"},{"key":"2026082509484990100_bib107","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1161\/CIRCRESAHA.119.316311","article-title":"Myofilament phosphorylation in stem cell treated diastolic heart failure","volume":"129","author":"Soetkamp","year":"2021","journal-title":"Circ. Res."},{"key":"2026082509484990100_bib108","doi-asserted-by":"publisher","first-page":"H1260","DOI":"10.1152\/ajpheart.1998.275.4.H1260","article-title":"BDM drives protein dephosphorylation and inhibits adenine nucleotide exchange in cardiomyocytes","volume":"275","author":"Stapleton","year":"1998","journal-title":"Am. J. Physiol."},{"key":"2026082509484990100_bib109","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.yjmcc.2025.10.008","article-title":"Molecular mechanisms of altered contraction with the beta-myosin R403Q mutation in porcine ventricular muscle and a human stem cell-derived cardiomyocyte model","volume":"209","author":"Steczina","year":"2025","journal-title":"J. Mol. Cell Cardiol."},{"key":"2026082509484990100_bib110","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1073\/pnas.0909468107","article-title":"Myosin ATP turnover rate is a mechanism involved in thermogenesis in resting skeletal muscle fibers","volume":"107","author":"Stewart","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026082509484990100_bib111","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.yjmcc.2012.12.010","article-title":"Microtubule proliferation in right ventricular myocytes of rats with monocrotaline-induced pulmonary hypertension","volume":"56","author":"Stones","year":"2013","journal-title":"J. Mol. Cell Cardiol"},{"key":"2026082509484990100_bib112","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1161\/01.cir.96.4.1313","article-title":"Failure to maintain a low ADP concentration impairs diastolic function in hypertrophied rat hearts","volume":"96","author":"Tian","year":"1997","journal-title":"Circulation"},{"key":"2026082509484990100_bib113","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1161\/CIRCULATIONAHA.119.042339","article-title":"Myosin sequestration regulates sarcomere function, cardiomyocyte energetics, and metabolism, informing the pathogenesis of hypertrophic cardiomyopathy","volume":"141","author":"Toepfer","year":"2020","journal-title":"Circulation"},{"key":"2026082509484990100_bib114","doi-asserted-by":"publisher","first-page":"5237","DOI":"10.1113\/JP272441","article-title":"Revisiting frank-starling: Regulatory light chain phosphorylation alters the rate of force redevelopment (ktr ) in a length-dependent fashion","volume":"594","author":"Toepfer","year":"2016","journal-title":"J. Physiol."},{"key":"2026082509484990100_bib115","doi-asserted-by":"publisher","first-page":"1629","DOI":"10.1161\/CIRCRESAHA.120.317046","article-title":"NAD+ repletion reverses heart failure with preserved ejection fraction","volume":"128","author":"Tong","year":"2021","journal-title":"Circ. Res."},{"key":"2026082509484990100_bib116","doi-asserted-by":"publisher","first-page":"1769","DOI":"10.1161\/CIRCULATIONAHA.119.042267","article-title":"Female sex is protective in a preclinical model of heart failure with preserved ejection fraction","volume":"140","author":"Tong","year":"2019","journal-title":"Circulation"},{"key":"2026082509484990100_bib117","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1126\/science.8097594","article-title":"Cytoskeletal role in the contractile dysfunction of hypertrophied myocardium","volume":"260","author":"Tsutsui","year":"1993","journal-title":"Science"},{"key":"2026082509484990100_bib118","doi-asserted-by":"publisher","first-page":"966968","DOI":"10.3389\/fcvm.2022.966968","article-title":"Proteomic and phosphoproteomic profiling in heart failure with preserved ejection fraction (HFpEF)","volume":"9","author":"Valero-Munoz","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"2026082509484990100_bib119","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1007\/s11897-012-0109-5","article-title":"Molecular and cellular basis for diastolic dysfunction","volume":"9","author":"Van Heerebeek","year":"2012","journal-title":"Curr. Heart Fail Rep."},{"key":"2026082509484990100_bib120","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1161\/CIRCULATIONAHA.111.076075","article-title":"Low myocardial protein kinase G activity in heart failure with preserved ejection fraction","volume":"126","author":"Van Heerebeek","year":"2012","journal-title":"Circulation"},{"key":"2026082509484990100_bib121","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1006\/jsbi.2002.4458","article-title":"Different molecular mechanics displayed by titin's constitutively and differentially expressed tandem Ig segments","volume":"137","author":"Watanabe","year":"2002","journal-title":"J. Struct. Biol."},{"key":"2026082509484990100_bib122","doi-asserted-by":"publisher","first-page":"1298","DOI":"10.1016\/j.jacbts.2023.05.012","article-title":"The cardioprotective effects of semaglutide exceed those of dietary weight loss in mice with HFpEF","volume":"8","author":"Withaar","year":"2023","journal-title":"JACC Basic Transl Sci."},{"key":"2026082509484990100_bib123","doi-asserted-by":"publisher","first-page":"2297","DOI":"10.1016\/S0006-3495(01)75876-6","article-title":"Titin-actin interaction in mouse myocardium: Passive tension modulation and its regulation by calcium\/S100A1","volume":"81","author":"Yamasaki","year":"2001","journal-title":"Biophys. J."},{"key":"2026082509484990100_bib124","doi-asserted-by":"publisher","first-page":"1953","DOI":"10.1056\/NEJMoa032566","article-title":"Diastolic heart failure--abnormalities in active relaxation and passive stiffness of the left ventricle","volume":"350","author":"Zile","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"2026082509484990100_bib125","doi-asserted-by":"publisher","first-page":"1247","DOI":"10.1161\/CIRCULATIONAHA.114.013215","article-title":"Myocardial stiffness in patients with heart failure and a preserved ejection fraction: Contributions of collagen and titin","volume":"131","author":"Zile","year":"2015","journal-title":"Circulation"}],"container-title":["Journal of General Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jgp\/article-pdf\/doi\/10.1085\/jgp.202614028\/2040136\/jgp_202614028.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jgp\/article-pdf\/doi\/10.1085\/jgp.202614028\/2040136\/jgp_202614028.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T13:48:58Z","timestamp":1787665738000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jgp\/article\/158\/6\/e202614028\/282972\/Diastolic-contributors-in-cardiomyocytes-of-a"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,25]]},"references-count":126,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,11,2]]}},"URL":"https:\/\/doi.org\/10.1085\/jgp.202614028","relation":{},"ISSN":["0022-1295","1540-7748"],"issn-type":[{"value":"0022-1295","type":"print"},{"value":"1540-7748","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,25]]},"article-number":"e202614028"}}