ArticleCirculation research2013
An endogenously produced fragment of cardiac myosin-binding protein C is pathogenic and can lead to heart failure.
Article in Circulation research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 31 citations in OpenAlex.
- Biomarker Profiling of Cardiac Causes for Chest Pain in Non-acute Coronary Syndrome Patients in West Virginia.Cureus · 2026Article
- Hypertrophic cardiomyopathy inThe journal of cardiovascular aging · 2024Article
- Myocardial Fibrosis in Hypertrophic Cardiomyopathy: A Perspective from Fibroblasts.International journal of molecular sciences · 2023Review
- Amino terminus of cardiac myosin binding protein-C regulates cardiac contractility.Journal of molecular and cellular cardiology · 2021Article
- AAV9 gene transfer of cMyBPC N-terminal domains ameliorates cardiomyopathy in cMyBPC-deficient mice.JCI insight · 2020Article
- Genetic, clinical, molecular, and pathogenic aspects of the South Asian-specific polymorphic MYBPC3Biophysical reviews · 2020Review
- Biomarkers for Heart Failure Prognosis: Proteins, Genetic Scores and Non-coding RNAs.Frontiers in cardiovascular medicine · 2020Review
- Ablation of the calpain-targeted site in cardiac myosin binding protein-C is cardioprotective during ischemia-reperfusion injury.Journal of molecular and cellular cardiology · 2019Article
- MYBPC3 truncation mutations enhance actomyosin contractile mechanics in human hypertrophic cardiomyopathy.Journal of molecular and cellular cardiology · 2019Article
- Recovery of left ventricular function following in vivo reexpression of cardiac myosin binding protein C.The Journal of general physiology · 2019Article
- Myofibroblast-Specific TGFβ Receptor II Signaling in the Fibrotic Response to Cardiac Myosin Binding Protein C-Induced Cardiomyopathy.Circulation research · 2018Article
- The Cardiac Myofibroblast.Circulation research · 2018Article
- Cardiac myosin-binding protein C is a novel marker of myocardial injury and fibrosis in aortic stenosis.Heart (British Cardiac Society) · 2018Article
- MMI-0100 Inhibits Cardiac Fibrosis in a Mouse Model Overexpressing Cardiac Myosin Binding Protein C.Journal of the American Heart Association · 2017Article
- Quantifying the Release of Biomarkers of Myocardial Necrosis from Cardiac Myocytes and Intact Myocardium.Clinical chemistry · 2017Article
- Diagnostic and Prognostic Value of Plasma Levels of Cardiac Myosin Binding Protein-C as a Novel Biomarker in Heart Failure.Pediatric cardiology · 2017Article
- N-terminal fragment of cardiac myosin binding protein-C triggers pro-inflammatory responses in vitro.Journal of molecular and cellular cardiology · 2016Article
- The A31P missense mutation in cardiac myosin binding protein C alters protein structure but does not cause haploinsufficiency.Archives of biochemistry and biophysics · 2016Article
- Alterations in Multi-Scale Cardiac Architecture in Association With Phosphorylation of Myosin Binding Protein-C.Journal of the American Heart Association · 2016Article
- Intensity matters: Ryanodine receptor regulation during exercise.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
rationaleA stable 40-kDa fragment is produced from cardiac myosin-binding protein C when the heart is stressed using a stimulus, such as ischemia-reperfusion injury. Elevated levels of the fragment can be detected in the diseased mouse and human heart, but its ability to interfere with normal cardiac function in the intact animal is unexplored.
objectiveTo understand the potential pathogenicity of the 40-kDa fragment in vivo and to investigate the molecular pathways that could be targeted for potential therapeutic intervention. METHODS AND
resultsWe generated cardiac myocyte-specific transgenic mice using a Tet-Off inducible system to permit controlled expression of the 40-kDa fragment in cardiomyocytes. When expression of the 40-kDa protein is induced by crossing the responder animals with tetracycline transactivator mice under conditions in which substantial quantities approximating those observed in diseased hearts are reached, the double-transgenic mice subsequently experience development of sarcomere dysgenesis and altered cardiac geometry, and the heart fails between 12 and 17 weeks of age. The induced double-transgenic mice had development of cardiac hypertrophy with myofibrillar disarray and fibrosis, in addition to activation of pathogenic MEK-ERK pathways. Inhibition of MEK-ERK signaling was achieved by injection of the mitogen-activated protein kinase (MAPK)/ERK inhibitor U0126. The drug effectively improved cardiac function, normalized heart size, and increased probability of survival.
conclusionsThese results suggest that the 40-kDa cardiac myosin-binding protein C fragment, which is produced at elevated levels during human cardiac disease, is a pathogenic fragment that is sufficient to cause hypertrophic cardiomyopathy and heart failure.
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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.