ArticleJCI insight2020
Modulating the tension-time integral of the cardiac twitch prevents dilated cardiomyopathy in murine hearts.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- The E525K β-Myosin Mutation Causes Hypocontractility in Cardiomyocytes Without Altering Loaded Crossbridge Cycling.bioRxiv : the preprint server for biology · 2026Article
- Hearts may grow concentrically to balance ATP supply and demand and eccentrically to stabilize titin-based stress.bioRxiv : the preprint server for biology · 2026Article
- Preventing hypocontractility-induced fibroblast expansion alleviates dilated cardiomyopathy.Science (New York, N.Y.) · 2025Article
- Echocardiographic Assessment of Cardiac Function in Mouse Models of Heart Disease.International journal of molecular sciences · 2025Review
- Screening single nucleotide changes to tropomyosin to identify novel cardiomyopathy mutants.Journal of molecular and cellular cardiology · 2025Article
- Article
- Bayesian estimation of muscle mechanisms and therapeutic targets using variational autoencoders.Biophysical journal · 2025Article
- Reduction in myofilament CaFrontiers in physiology · 2025Article
- Bayesian Estimation of Muscle Mechanisms and Therapeutic Targets Using Variational Autoencoders.bioRxiv : the preprint server for biology · 2024Article
- Mechanisms of a novel regulatory light chain-dependent cardiac myosin inhibitor.The Journal of general physiology · 2024Article
- Emerging Concepts of Mechanisms Controlling Cardiac Tension: Focus on Familial Dilated Cardiomyopathy (DCM) and Sarcomere-Directed Therapies.Biomedicines · 2024Review
- In silico and in vitro models reveal the molecular mechanisms of hypocontractility caused byFrontiers in physiology · 2024Article
- Danicamtiv Increases Myosin Recruitment and Alters Cross-Bridge Cycling in Cardiac Muscle.Circulation research · 2023Article
- Mouse Models of Cardiomyopathies Caused by Mutations in Troponin C.International journal of molecular sciences · 2023Review
- Machine learning meets Monte Carlo methods for models of muscle's molecular machinery to classify mutations.The Journal of general physiology · 2023Article
- dATP elevation induces myocardial metabolic remodeling to support improved cardiac function.Journal of molecular and cellular cardiology · 2023Article
- Signaling network model of cardiomyocyte morphological changes in familial cardiomyopathy.Journal of molecular and cellular cardiology · 2023Article
- Effect of Myosin Isoforms on Cardiac Muscle Twitch of Mice, Rats and Humans.International journal of molecular sciences · 2022Article
- Subcellular Remodeling in Filamin C Deficient Mouse Hearts Impairs Myocyte Tension Development during Progression of Dilated Cardiomyopathy.International journal of molecular sciences · 2022Article
- Thin filament cardiomyopathies: A review of genetics, disease mechanisms, and emerging therapeutics.Frontiers in cardiovascular medicine · 2022Review
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Dilated cardiomyopathy (DCM) is often associated with sarcomere protein mutations that confer reduced myofilament tension-generating capacity. We demonstrated that cardiac twitch tension-time integrals can be targeted and tuned to prevent DCM remodeling in hearts with contractile dysfunction. We employed a transgenic murine model of DCM caused by the D230N-tropomyosin (Tm) mutation and designed a sarcomere-based intervention specifically targeting the twitch tension-time integral of D230N-Tm hearts using multiscale computational models of intramolecular and intermolecular interactions in the thin filament and cell-level contractile simulations. Our models predicted that increasing the calcium sensitivity of thin filament activation using the cardiac troponin C (cTnC) variant L48Q can sufficiently augment twitch tension-time integrals of D230N-Tm hearts. Indeed, cardiac muscle isolated from double-transgenic hearts expressing D230N-Tm and L48Q cTnC had increased calcium sensitivity of tension development and increased twitch tension-time integrals compared with preparations from hearts with D230N-Tm alone. Longitudinal echocardiographic measurements revealed that DTG hearts retained normal cardiac morphology and function, whereas D230N-Tm hearts developed progressive DCM. We present a computational and experimental framework for targeting molecular mechanisms governing the twitch tension of cardiomyopathic hearts to counteract putative mechanical drivers of adverse remodeling and open possibilities for tension-based treatments of genetic cardiomyopathies.
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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.