ArticleJournal of molecular and cellular cardiology2012
Increased myofilament Ca2+ sensitivity and diastolic dysfunction as early consequences of Mybpc3 mutation in heterozygous knock-in mice.
Article in Journal of molecular and cellular cardiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 2 of them syntheses that pooled it.
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Who cites it
97 citing papers in PubMed, 2 syntheses or guidelines pooled it, 136 citations in OpenAlex.
- Cardiomyopathy phenotypes in human-induced pluripotent stem cell-derived cardiomyocytes-a systematic review.Pflugers Archiv : European journal of physiology · 2019Pooled it
- Clinical outcomes associated with sarcomere mutations in hypertrophic cardiomyopathy: a meta-analysis on 7675 individuals.Clinical research in cardiology : official journal of the German Cardiac Society · 2018Pooled it
- Biomechanical stress unmasks a fibroblast-dependent hypercontractile-disarray phenotype in MYBPC3 truncation HCM.APL bioengineering · 2026Article
- 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 mechanotransduction from development to disease.APL bioengineering · 2026Review
- The Potential Protective Effects of Resveratrol Against Cabazitaxel-Induced Oxidative Stress and Cardiotoxicity in Rats.Cardiovascular toxicology · 2026Article
- Variable cMyBP-C expression from cell to cell in a MYBPC3Stem cell research & therapy · 2026Article
- Hypercontractility and Oxidative Stress Drive Creatine Kinase Dysfunction in Hypertrophic Cardiomyopathy.Circulation · 2025Article
- Concomitant changes in regional myocardial deformation and intraventricular pressure gradients in normal and sedated goats: advanced multimodal echocardiographic study.BMC veterinary research · 2025Article
- Evaluation of sudden cardiac death in hypertrophic cardiomyopathy.Journal of cardiovascular imaging · 2025Review
- Atrial cardiomyopathy resulting from loss of plakophilin-2 expression: Response to adrenergic stimulation and implications for the exercise response.The Journal of physiology · 2025Article
- An organ-wide spatiotemporal transcriptomic and cellular atlas of the regenerating zebrafish heart.Nature communications · 2025Article
- Substrates of Sudden Cardiac Death in Hypertrophic Cardiomyopathy.Journal of clinical medicine · 2025Review
- Cardiac MRI Strain as an Early Indicator of Myocardial Dysfunction in Hypertrophic Cardiomyopathy.International journal of molecular sciences · 2025Article
- Hyperpolarized-MRI in Hypertrophic Cardiomyopathy: A Narrative Review.Clinical Medicine Insights. Cardiology · 2025Review
- Obstructive hypertrophic cardiomyopathy: from genetic insights to a multimodal therapeutic approach with mavacamten, aficamten, and beyond.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2024Review
- Arg92Leu-cTnT Alters the cTnC-cTnI Interface Disrupting PKA-Mediated Relaxation.Circulation research · 2024Article
- Chronic Activation of Tubulin Tyrosination Improves Heart Function.Circulation research · 2024Article
- Current perspectives of sudden cardiac death management in hypertrophic cardiomyopathy.Heart failure reviews · 2024Review
- Hypertrophic cardiomyopathy inThe journal of cardiovascular aging · 2024Article
37 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 8 institutions in 3 countries.
Funding
Abstract
Hypertrophic cardiomyopathy (HCM) is frequently caused by mutations in MYBPC3 encoding cardiac myosin-binding protein C (cMyBP-C). The mechanisms leading from gene mutations to the HCM phenotype remain incompletely understood, partially because current mouse models of HCM do not faithfully reflect the human situation and early hypertrophy confounds the interpretation of functional alterations. The goal of this study was to evaluate whether myofilament Ca(2+) sensitization and diastolic dysfunction are associated or precede the development of left ventricular hypertrophy (LVH) in HCM. We evaluated the function of skinned and intact cardiac myocytes, as well as the intact heart in a recently developed Mybpc3-targeted knock-in mouse model carrying a point mutation frequently associated with HCM. Compared to wild-type, 10-week old homozygous knock-in mice exhibited i) higher myofilament Ca(2+) sensitivity in skinned ventricular trabeculae, ii) lower diastolic sarcomere length, and faster Ca(2+) transient decay in intact myocytes, and iii) LVH, reduced fractional shortening, lower E/A and E'/A', and higher E/E' ratios by echocardiography and Doppler analysis, suggesting systolic and diastolic dysfunction. In contrast, heterozygous knock-in mice, which mimic the human HCM situation, did not exhibit LVH or systolic dysfunction, but exhibited higher myofilament Ca(2+) sensitivity, faster Ca(2+) transient decay, and diastolic dysfunction. These data demonstrate that myofilament Ca(2+) sensitization and diastolic dysfunction are early phenotypic consequences of Mybpc3 mutations independent of LVH. The accelerated Ca(2+) transients point to compensatory mechanisms directed towards normalization of relaxation. We propose that HCM is a model for diastolic heart failure and this mouse model could be valuable in studying mechanisms and treatment modalities.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.