ArticleCardiovascular research2019
Altered C10 domain in cardiac myosin binding protein-C results in hypertrophic cardiomyopathy.
Article in Cardiovascular research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
- Myosin motor dynamics and cardiac function: Insights from in vivo small-angle X-ray scattering and pressure-volume analysis.The Journal of physiology · 2026Article
- Cardiac myosin-binding protein C: potential early biomarker of myocardial injury in coronary artery bypass surgery.Journal of cardiothoracic surgery · 2026Article
- Hypertrophic cardiomyopathy: comprehensive insights into pathogenic genes and genotype-phenotype associations.Frontiers in cell and developmental biology · 2026Review
- Cardiomyocyte Nuclear Pleomorphism in a Mouse Model of Inherited Hypertrophic Cardiomyopathy.Journal of cardiovascular development and disease · 2025Article
- Myocardial dysfunction caused by MyBPC3 P459fs mutation in hypertrophic cardiomyopathy: evidence from multi-omics approaches and super-resolution imaging.Frontiers in cardiovascular medicine · 2025Article
- The D75N and P161S Mutations in the C0-C2 Fragment of cMyBP-C Associated with Hypertrophic Cardiomyopathy Disturb the Thin Filament Activation, Nucleotide Exchange in Myosin, and Actin-Myosin Interaction.International journal of molecular sciences · 2024Article
- Roles of cMyBP-C phosphorylation on cardiac contractile dysfunction inJournal of molecular and cellular cardiology plus · 2024Article
- Sleep fragmentation induces heart failure in a hypertrophic cardiomyopathy mouse model by altering redox metabolism.iScience · 2024Article
- Hypertrophic cardiomyopathy inThe journal of cardiovascular aging · 2024Article
- Myofilament dysfunction in diastolic heart failure.Heart failure reviews · 2024Review
- Astragaloside IV derivative HHQ16 ameliorates infarction-induced hypertrophy and heart failure through degradation of lncRNA4012/9456.Signal transduction and targeted therapy · 2023Article
- Sarcomeric gene variants among Indians with hypertrophic cardiomyopathy: A scoping review.The Indian journal of medical research · 2023Article
- An Update on MYBPC3 Gene Mutation in Hypertrophic Cardiomyopathy.International journal of molecular sciences · 2023Review
- Is haploinsufficiency a sufficient mechanism for MYBPC3 truncating mutations?The Journal of general physiology · 2023Article
- Myofilament Alterations Associated with Human R14del-Phospholamban Cardiomyopathy.International journal of molecular sciences · 2023Article
- Kelch-like protein 3 in human disease and therapy.Molecular biology reports · 2022Review
- Mass-Spectrometry-Based Functional Proteomic and Phosphoproteomic Technologies and Their Application for Analyzing Ex Vivo and In Vitro Models of Hypertrophic Cardiomyopathy.International journal of molecular sciences · 2021Review
- Assessment of the Contribution of a Thermodynamic and Mechanical Destabilization of Myosin-Binding Protein C Domain C2 to the Pathomechanism of Hypertrophic Cardiomyopathy-Causing Double MutationInternational journal of molecular sciences · 2021Article
- Amino terminus of cardiac myosin binding protein-C regulates cardiac contractility.Journal of molecular and cellular cardiology · 2021Article
- South Asian-SpecificFrontiers in cardiovascular medicine · 2021Article
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10 authors at 5 institutions in 2 countries.
Funding
Abstract
aimsA 25-base pair deletion in the cardiac myosin binding protein-C (cMyBP-C) gene (MYBPC3), proposed to skip exon 33, modifies the C10 domain (cMyBP-CΔC10mut) and is associated with hypertrophic cardiomyopathy (HCM) and heart failure, affecting approximately 100 million South Asians. However, the molecular mechanisms underlying the pathogenicity of cMyBP-CΔC10mutin vivo are unknown. We hypothesized that expression of cMyBP-CΔC10mut exerts a poison polypeptide effect leading to improper assembly of cardiac sarcomeres and the development of HCM. METHODS AND
resultsTo determine whether expression of cMyBP-CΔC10mut is sufficient to cause HCM and contractile dysfunction in vivo, we generated transgenic (TG) mice having cardiac-specific protein expression of cMyBP-CΔC10mut at approximately half the level of endogenous cMyBP-C. At 12 weeks of age, significant hypertrophy was observed in TG mice expressing cMyBP-CΔC10mut (heart weight/body weight ratio: 4.43 ± 0.11 mg/g non-transgenic (NTG) vs. 5.34 ± 0.25 mg/g cMyBP-CΔC10mut, P < 0.05). Furthermore, haematoxylin and eosin, Masson's trichrome staining, as well as second-harmonic generation imaging revealed the presence of significant fibrosis and a greater relative nuclear area in cMyBP-CΔC10mut hearts compared with NTG controls. M-mode echocardiography analysis revealed hypercontractile hearts (EF: 53.4%±2.9% NTG vs. 66.4% ± 4.7% cMyBP-CΔC10mut; P < 0.05) and early diastolic dysfunction (E/E': 28.7 ± 3.7 NTG vs. 46.3 ± 8.4 cMyBP-CΔC10mut; P < 0.05), indicating the presence of an HCM phenotype. To assess whether these changes manifested at the myofilament level, contractile function of single skinned cardiomyocytes was measured. Preserved maximum force generation and increased Ca2+-sensitivity of force generation were observed in cardiomyocytes from cMyBP-CΔC10mut mice compared with NTG controls (EC50: 3.6 ± 0.02 µM NTG vs. 2.90 ± 0.01 µM cMyBP-CΔC10mut; P < 0.0001).
conclusionExpression of cMyBP-C protein with a modified C10 domain is sufficient to cause contractile dysfunction and HCM in vivo.
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