2026-05-25T05:45:53Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/147002024-09-27T08:33:18Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Suay-Corredera, Carmen author Alegre-Cebollada, Jorge author 2022 Hypertrophic 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. FEBS Lett . 2022 Mar;596(6):703-746 10.1002/1873-3468.14301 1873-3468 0014-5793 FEBS letters 35224729 http://hdl.handle.net/20.500.12105/14700 The mechanics of the heart: zooming in on hypertrophic cardiomyopathy and cMyBP-C.