ArticleThe Journal of physiology2014
Faster cross-bridge detachment and increased tension cost in human hypertrophic cardiomyopathy with the R403Q MYH7 mutation.
Article in The Journal of physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 84 citations in OpenAlex.
- Effect of trimetazidine dihydrochloride therapy on myocardial external efficiency in pre-clinical individuals with a hypertrophic cardiomyopathy pathogenic variant: results of the ENERGY trial.Cardiovascular research · 2025Trial
- Immature and mature myocardium in the pathophysiology of hypertrophic cardiomyopathy.Journal of molecular and cellular cardiology plus · 2026Review
- Biomechanical stress unmasks a fibroblast-dependent hypercontractile-disarray phenotype in MYBPC3 truncation HCM.APL bioengineering · 2026Article
- Probing relaxed myosin states in hypertrophic cardiomyopathy by second harmonic-generation microscopy.eLife · 2026Article
- Obscurin deficiency leads to compensated dilated cardiomyopathy and increased arrhythmias.The Journal of general physiology · 2025Article
- Hypertrophic Cardiomyopathy Through the Lens of Mitochondria.Biomedicines · 2025Review
- Definitional Challenges in Understanding Hypertrophic Cardiomyopathy.Diagnostics (Basel, Switzerland) · 2024Review
- 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
- Allele-specific dysregulation of lipid and energy metabolism in early-stage hypertrophic cardiomyopathy.Journal of molecular and cellular cardiology plus · 2024Article
- Incomplete-penetrant hypertrophic cardiomyopathyProceedings of the National Academy of Sciences of the United States of America · 2024Article
- A Laing distal myopathy-associated proline substitution in the β-myosin rod perturbs myosin cross-bridging activity.The Journal of clinical investigation · 2024Article
- Mechano-energetic uncoupling in hypertrophic cardiomyopathy: Pathophysiological mechanisms and therapeutic opportunities.Journal of molecular and cellular cardiology plus · 2023Review
- Mitochondrial dysfunction in human hypertrophic cardiomyopathy is linked to cardiomyocyte architecture disruption and corrected by improving NADH-driven mitochondrial respiration.European heart journal · 2023Article
- Slower Calcium Handling Balances Faster Cross-Bridge Cycling in HumanCirculation research · 2023Article
- Multi-Omics Profiling of Hypertrophic Cardiomyopathy Reveals Altered Mechanisms in Mitochondrial Dynamics and Excitation-Contraction Coupling.International journal of molecular sciences · 2023Article
- Reproducibility and reporting negative data.Journal of molecular and cellular cardiology plus · 2022Article
- Critical Evaluation of Current Hypotheses for the Pathogenesis of Hypertrophic Cardiomyopathy.International journal of molecular sciences · 2022Review
- Prospects for remodeling the hypertrophic heart with myosin modulators.Frontiers in cardiovascular medicine · 2022Review
- Genotype-Driven Pathogenesis of Atrial Fibrillation in Hypertrophic Cardiomyopathy: The Case of DifferentFrontiers in physiology · 2022Article
- Alpha and beta myosin isoforms and human atrial and ventricular contraction.Cellular and molecular life sciences : CMLS · 2021Review
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 5 countries.
Funding
Abstract
The first mutation associated with hypertrophic cardiomyopathy (HCM) is the R403Q mutation in the gene encoding β-myosin heavy chain (β-MyHC). R403Q locates in the globular head of myosin (S1), responsible for interaction with actin, and thus motor function of myosin. Increased cross-bridge relaxation kinetics caused by the R403Q mutation might underlie increased energetic cost of tension generation; however, direct evidence is absent. Here we studied to what extent cross-bridge kinetics and energetics are related in single cardiac myofibrils and multicellular cardiac muscle strips of three HCM patients with the R403Q mutation and nine sarcomere mutation-negative HCM patients (HCMsmn). Expression of R403Q was on average 41 ± 4% of total MYH7 mRNA. Cross-bridge slow relaxation kinetics in single R403Q myofibrils was significantly higher (P < 0.0001) than in HCMsmn myofibrils (0.47 ± 0.02 and 0.30 ± 0.02 s(-1), respectively). Moreover, compared to HCMsmn, tension cost was significantly higher in the muscle strips of the three R403Q patients (2.93 ± 0.25 and 1.78 ± 0.10 μmol l(-1) s(-1) kN(-1) m(-2), respectively) which showed a positive linear correlation with relaxation kinetics in the corresponding myofibril preparations. This correlation suggests that faster cross-bridge relaxation kinetics results in an increase in energetic cost of tension generation in human HCM with the R403Q mutation compared to HCMsmn. Therefore, increased tension cost might contribute to HCM disease in patients carrying the R403Q mutation.
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