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dc.contributor.authorSuay-Corredera, Carmen 
dc.contributor.authorAlegre-Cebollada, Jorge
dc.identifier.citationFEBS Lett . 2022 Mar;596(6):703-746es_ES
dc.description.abstractHypertrophic cardiomyopathy (HCM), a disease characterized by cardiac muscle hypertrophy and hypercontractility, is the most frequently inherited disorder of the heart. HCM is mainly caused by variants in genes encoding proteins of the sarcomere, the basic contractile unit of cardiomyocytes. The most frequently mutated among them is MYBPC3, which encodes cardiac myosin-binding protein C (cMyBP-C), a key regulator of sarcomere contraction. In this review, we summarize clinical and genetic aspects of HCM and provide updated information on the function of the healthy and HCM sarcomere, as well as on emerging therapeutic options targeting sarcomere mechanical activity. Building on what is known about cMyBP-C activity, we examine different pathogenicity drivers by which MYBPC3 variants can cause disease, focussing on protein haploinsufficiency as a common pathomechanism also in nontruncating variants. Finally, we discuss recent evidence correlating altered cMyBP-C mechanical properties with HCM development.es_ES
dc.description.sponsorshipResearch in our laboratory on HCM pathomechanisms induced by MYBPC3 variants is funded by the Spanish Ministry of Science and Innovation (MCIN/AEI/10.13039/501100011033) through grant PID2020120426GB-I00 and the Severo Ochoa Program for Centers of Excellence in R&D in its 2015 and 2020 calls (ref. SEV-2015-0505 and ref. CEX2020-001041-S); and by consortium Tec4Bio-CM (S2018/NMT-4443) from the Comunidad de Madrid. This last call is 50% co-financed by the European Social Fund (ESF) and the European Regional Development Fund (ERDF) for the programming period 2014-2020. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), MCIN and the Pro CNIC Foundation. CS-C is the recipient of an FPI-SO predoctoral fellowship BES-2016-076638. We thank Eli ' as Herrero-Gal ' an for critical feedback. We thank Metello Innocenti for editorial feedback. We thank two anonymous reviewers for their expert feedback.es_ES
dc.subject.meshCardiomyopathy, Hypertrophices_ES
dc.subject.meshCarrier Proteins es_ES
dc.subject.meshCytoskeletal Proteins es_ES
dc.subject.meshHumans es_ES
dc.subject.meshMutation es_ES
dc.subject.meshMyocytes, Cardiaces_ES
dc.subject.meshSarcomeres es_ES
dc.titleThe mechanics of the heart: zooming in on hypertrophic cardiomyopathy and cMyBP-C.es_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.journalFEBS letterses_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Mecánica molecular del sistema cardiovasculares_ES
dc.rights.accessRightsopen accesses_ES

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Atribución 4.0 Internacional
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