ArticleCirculation. Heart failure2015
Phosphorylation of cardiac Myosin-binding protein-C is a critical mediator of diastolic function.
Open access · bronzeAbstract readComparative Study
In one paragraph
Article in Circulation. Heart failure, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed, 1 pooled it
7.9field-weighted citation impact, top 2% of its field
What it found
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Who cites it
80 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- Implications of S-glutathionylation of sarcomere proteins in cardiac disorders, therapies, and diagnosis.Frontiers in cardiovascular medicine · 2022Pooled it
- Evidence for a role of adverse sarcomere signaling in atrial fibrillation induction.Journal of molecular and cellular cardiology plus · 2026Review
- Diastolic contributors in cardiomyocytes of a cardiometabolic HFpEF-like mouse model.The Journal of general physiology · 2026Article
- Fast skeletal myosin binding protein-C expression exacerbates dysfunction in heart failure.Basic research in cardiology · 2026Article
- Cardiac myosin-binding protein-C acts as a tunable load sensor to regulate afterload dependence of ventricular function.American journal of physiology. Heart and circulatory physiology · 2025Article
- A new era of understanding of the control of thick filament states in the heartbeat.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Myosin binding protein-C modulates loaded sarcomere shortening in rodent permeabilized cardiac myocytes.The Journal of general physiology · 2025Article
- Article
- cMyBP-C in hypertrophic cardiomyopathy: gene therapy and small-molecule innovations.Frontiers in cardiovascular medicine · 2025Review
- Genetic Basis of Hypertrophic Cardiomyopathy in Cats.Current issues in molecular biology · 2024Review
- Alterations in cardiac contractile and regulatory proteins contribute to age-related cardiac dysfunction in male rats.Physiological reports · 2024Article
- Acute Biomechanical Effects of Empagliflozin on Living Isolated Human Heart Failure Myocardium.Cardiovascular drugs and therapy · 2024Article
- Roles of cMyBP-C phosphorylation on cardiac contractile dysfunction inJournal of molecular and cellular cardiology plus · 2024Article
- Hypertrophic cardiomyopathy dysfunction mimicked in human engineered heart tissue and improved by sodium-glucose cotransporter 2 inhibitors.Cardiovascular research · 2024Article
- Cardiac myosin-binding protein C N-terminal interactions with myosin and actin filaments: Opposite effects of phosphorylation and M-domain mutations.Journal of molecular and cellular cardiology · 2024Article
- Hypertrophic cardiomyopathy inThe journal of cardiovascular aging · 2024Article
- Bringing into focus the central domains C3-C6 of myosin binding protein C.Frontiers in physiology · 2024Review
- Signalling of Adrenoceptors: Canonical Pathways and New Paradigms.Handbook of experimental pharmacology · 2024Review
- Hypertrophic cardiomyopathy in purpose-bred cats with the A31P mutation in cardiac myosin binding protein-C.Scientific reports · 2023Article
- The contribution of N-terminal truncated cMyBPC to in vivo cardiac function.The Journal of general physiology · 2023Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 2 institutions in 1 country.
Paola C RosasFrom the Department of Medical Physiology (P.C.R., Y.L., M.I.A., B.M.M., C.W.T.) and Division of Molecular Cardiology, Department of Medicine (C.M.T., R.K., K.M.B.), Texas A&M University Health Science Center, College of Medicine, Temple City; Internal Medicine/Division of Cardiology (D.T.K., C.W.T.) and Department of Surgery (G.F.D., D.M.), Baylor Scott & White Health-Central Texas, Temple City; Department of Cell and Regenerative Biology and Biotechnology Center, University of Wisconsin School of Medicine and Public Health, Madison (P.A.P., D.P.F., R.L.M.); and Department of Physiology and Biophysics and Center for Cardiovascular Research, College of Medicine, University of Illinois, Chicago (B.G.P., C.M.W., R.J.S.).
Yang LiuFrom the Department of Medical Physiology (P.C.R., Y.L., M.I.A., B.M.M., C.W.T.) and Division of Molecular Cardiology, Department of Medicine (C.M.T., R.K., K.M.B.), Texas A&M University Health Science Center, College of Medicine, Temple City; Internal Medicine/Division of Cardiology (D.T.K., C.W.T.) and Department of Surgery (G.F.D., D.M.), Baylor Scott & White Health-Central Texas, Temple City; Department of Cell and Regenerative Biology and Biotechnology Center, University of Wisconsin School of Medicine and Public Health, Madison (P.A.P., D.P.F., R.L.M.); and Department of Physiology and Biophysics and Center for Cardiovascular Research, College of Medicine, University of Illinois, Chicago (B.G.P., C.M.W., R.J.S.).
Mohamed I AbdallaFrom the Department of Medical Physiology (P.C.R., Y.L., M.I.A., B.M.M., C.W.T.) and Division of Molecular Cardiology, Department of Medicine (C.M.T., R.K., K.M.B.), Texas A&M University Health Science Center, College of Medicine, Temple City; Internal Medicine/Division of Cardiology (D.T.K., C.W.T.) and Department of Surgery (G.F.D., D.M.), Baylor Scott & White Health-Central Texas, Temple City; Department of Cell and Regenerative Biology and Biotechnology Center, University of Wisconsin School of Medicine and Public Health, Madison (P.A.P., D.P.F., R.L.M.); and Department of Physiology and Biophysics and Center for Cardiovascular Research, College of Medicine, University of Illinois, Chicago (B.G.P., C.M.W., R.J.S.).
Candice M ThomasFrom the Department of Medical Physiology (P.C.R., Y.L., M.I.A., B.M.M., C.W.T.) and Division of Molecular Cardiology, Department of Medicine (C.M.T., R.K., K.M.B.), Texas A&M University Health Science Center, College of Medicine, Temple City; Internal Medicine/Division of Cardiology (D.T.K., C.W.T.) and Department of Surgery (G.F.D., D.M.), Baylor Scott & White Health-Central Texas, Temple City; Department of Cell and Regenerative Biology and Biotechnology Center, University of Wisconsin School of Medicine and Public Health, Madison (P.A.P., D.P.F., R.L.M.); and Department of Physiology and Biophysics and Center for Cardiovascular Research, College of Medicine, University of Illinois, Chicago (B.G.P., C.M.W., R.J.S.).
David T KidwellFrom the Department of Medical Physiology (P.C.R., Y.L., M.I.A., B.M.M., C.W.T.) and Division of Molecular Cardiology, Department of Medicine (C.M.T., R.K., K.M.B.), Texas A&M University Health Science Center, College of Medicine, Temple City; Internal Medicine/Division of Cardiology (D.T.K., C.W.T.) and Department of Surgery (G.F.D., D.M.), Baylor Scott & White Health-Central Texas, Temple City; Department of Cell and Regenerative Biology and Biotechnology Center, University of Wisconsin School of Medicine and Public Health, Madison (P.A.P., D.P.F., R.L.M.); and Department of Physiology and Biophysics and Center for Cardiovascular Research, College of Medicine, University of Illinois, Chicago (B.G.P., C.M.W., R.J.S.).
Giuseppina F DusioFrom the Department of Medical Physiology (P.C.R., Y.L., M.I.A., B.M.M., C.W.T.) and Division of Molecular Cardiology, Department of Medicine (C.M.T., R.K., K.M.B.), Texas A&M University Health Science Center, College of Medicine, Temple City; Internal Medicine/Division of Cardiology (D.T.K., C.W.T.) and Department of Surgery (G.F.D., D.M.), Baylor Scott & White Health-Central Texas, Temple City; Department of Cell and Regenerative Biology and Biotechnology Center, University of Wisconsin School of Medicine and Public Health, Madison (P.A.P., D.P.F., R.L.M.); and Department of Physiology and Biophysics and Center for Cardiovascular Research, College of Medicine, University of Illinois, Chicago (B.G.P., C.M.W., R.J.S.).
Dhriti MukhopadhyayFrom the Department of Medical Physiology (P.C.R., Y.L., M.I.A., B.M.M., C.W.T.) and Division of Molecular Cardiology, Department of Medicine (C.M.T., R.K., K.M.B.), Texas A&M University Health Science Center, College of Medicine, Temple City; Internal Medicine/Division of Cardiology (D.T.K., C.W.T.) and Department of Surgery (G.F.D., D.M.), Baylor Scott & White Health-Central Texas, Temple City; Department of Cell and Regenerative Biology and Biotechnology Center, University of Wisconsin School of Medicine and Public Health, Madison (P.A.P., D.P.F., R.L.M.); and Department of Physiology and Biophysics and Center for Cardiovascular Research, College of Medicine, University of Illinois, Chicago (B.G.P., C.M.W., R.J.S.).
Rajesh KumarFrom the Department of Medical Physiology (P.C.R., Y.L., M.I.A., B.M.M., C.W.T.) and Division of Molecular Cardiology, Department of Medicine (C.M.T., R.K., K.M.B.), Texas A&M University Health Science Center, College of Medicine, Temple City; Internal Medicine/Division of Cardiology (D.T.K., C.W.T.) and Department of Surgery (G.F.D., D.M.), Baylor Scott & White Health-Central Texas, Temple City; Department of Cell and Regenerative Biology and Biotechnology Center, University of Wisconsin School of Medicine and Public Health, Madison (P.A.P., D.P.F., R.L.M.); and Department of Physiology and Biophysics and Center for Cardiovascular Research, College of Medicine, University of Illinois, Chicago (B.G.P., C.M.W., R.J.S.).
Kenneth M BakerFrom the Department of Medical Physiology (P.C.R., Y.L., M.I.A., B.M.M., C.W.T.) and Division of Molecular Cardiology, Department of Medicine (C.M.T., R.K., K.M.B.), Texas A&M University Health Science Center, College of Medicine, Temple City; Internal Medicine/Division of Cardiology (D.T.K., C.W.T.) and Department of Surgery (G.F.D., D.M.), Baylor Scott & White Health-Central Texas, Temple City; Department of Cell and Regenerative Biology and Biotechnology Center, University of Wisconsin School of Medicine and Public Health, Madison (P.A.P., D.P.F., R.L.M.); and Department of Physiology and Biophysics and Center for Cardiovascular Research, College of Medicine, University of Illinois, Chicago (B.G.P., C.M.W., R.J.S.).
Brett M MitchellFrom the Department of Medical Physiology (P.C.R., Y.L., M.I.A., B.M.M., C.W.T.) and Division of Molecular Cardiology, Department of Medicine (C.M.T., R.K., K.M.B.), Texas A&M University Health Science Center, College of Medicine, Temple City; Internal Medicine/Division of Cardiology (D.T.K., C.W.T.) and Department of Surgery (G.F.D., D.M.), Baylor Scott & White Health-Central Texas, Temple City; Department of Cell and Regenerative Biology and Biotechnology Center, University of Wisconsin School of Medicine and Public Health, Madison (P.A.P., D.P.F., R.L.M.); and Department of Physiology and Biophysics and Center for Cardiovascular Research, College of Medicine, University of Illinois, Chicago (B.G.P., C.M.W., R.J.S.).
Patricia A PowersFrom the Department of Medical Physiology (P.C.R., Y.L., M.I.A., B.M.M., C.W.T.) and Division of Molecular Cardiology, Department of Medicine (C.M.T., R.K., K.M.B.), Texas A&M University Health Science Center, College of Medicine, Temple City; Internal Medicine/Division of Cardiology (D.T.K., C.W.T.) and Department of Surgery (G.F.D., D.M.), Baylor Scott & White Health-Central Texas, Temple City; Department of Cell and Regenerative Biology and Biotechnology Center, University of Wisconsin School of Medicine and Public Health, Madison (P.A.P., D.P.F., R.L.M.); and Department of Physiology and Biophysics and Center for Cardiovascular Research, College of Medicine, University of Illinois, Chicago (B.G.P., C.M.W., R.J.S.).
Daniel P FitzsimonsFrom the Department of Medical Physiology (P.C.R., Y.L., M.I.A., B.M.M., C.W.T.) and Division of Molecular Cardiology, Department of Medicine (C.M.T., R.K., K.M.B.), Texas A&M University Health Science Center, College of Medicine, Temple City; Internal Medicine/Division of Cardiology (D.T.K., C.W.T.) and Department of Surgery (G.F.D., D.M.), Baylor Scott & White Health-Central Texas, Temple City; Department of Cell and Regenerative Biology and Biotechnology Center, University of Wisconsin School of Medicine and Public Health, Madison (P.A.P., D.P.F., R.L.M.); and Department of Physiology and Biophysics and Center for Cardiovascular Research, College of Medicine, University of Illinois, Chicago (B.G.P., C.M.W., R.J.S.).
Bindiya G PatelFrom the Department of Medical Physiology (P.C.R., Y.L., M.I.A., B.M.M., C.W.T.) and Division of Molecular Cardiology, Department of Medicine (C.M.T., R.K., K.M.B.), Texas A&M University Health Science Center, College of Medicine, Temple City; Internal Medicine/Division of Cardiology (D.T.K., C.W.T.) and Department of Surgery (G.F.D., D.M.), Baylor Scott & White Health-Central Texas, Temple City; Department of Cell and Regenerative Biology and Biotechnology Center, University of Wisconsin School of Medicine and Public Health, Madison (P.A.P., D.P.F., R.L.M.); and Department of Physiology and Biophysics and Center for Cardiovascular Research, College of Medicine, University of Illinois, Chicago (B.G.P., C.M.W., R.J.S.).
Chad M WarrenFrom the Department of Medical Physiology (P.C.R., Y.L., M.I.A., B.M.M., C.W.T.) and Division of Molecular Cardiology, Department of Medicine (C.M.T., R.K., K.M.B.), Texas A&M University Health Science Center, College of Medicine, Temple City; Internal Medicine/Division of Cardiology (D.T.K., C.W.T.) and Department of Surgery (G.F.D., D.M.), Baylor Scott & White Health-Central Texas, Temple City; Department of Cell and Regenerative Biology and Biotechnology Center, University of Wisconsin School of Medicine and Public Health, Madison (P.A.P., D.P.F., R.L.M.); and Department of Physiology and Biophysics and Center for Cardiovascular Research, College of Medicine, University of Illinois, Chicago (B.G.P., C.M.W., R.J.S.).
R John SolaroFrom the Department of Medical Physiology (P.C.R., Y.L., M.I.A., B.M.M., C.W.T.) and Division of Molecular Cardiology, Department of Medicine (C.M.T., R.K., K.M.B.), Texas A&M University Health Science Center, College of Medicine, Temple City; Internal Medicine/Division of Cardiology (D.T.K., C.W.T.) and Department of Surgery (G.F.D., D.M.), Baylor Scott & White Health-Central Texas, Temple City; Department of Cell and Regenerative Biology and Biotechnology Center, University of Wisconsin School of Medicine and Public Health, Madison (P.A.P., D.P.F., R.L.M.); and Department of Physiology and Biophysics and Center for Cardiovascular Research, College of Medicine, University of Illinois, Chicago (B.G.P., C.M.W., R.J.S.).
Richard L MossFrom the Department of Medical Physiology (P.C.R., Y.L., M.I.A., B.M.M., C.W.T.) and Division of Molecular Cardiology, Department of Medicine (C.M.T., R.K., K.M.B.), Texas A&M University Health Science Center, College of Medicine, Temple City; Internal Medicine/Division of Cardiology (D.T.K., C.W.T.) and Department of Surgery (G.F.D., D.M.), Baylor Scott & White Health-Central Texas, Temple City; Department of Cell and Regenerative Biology and Biotechnology Center, University of Wisconsin School of Medicine and Public Health, Madison (P.A.P., D.P.F., R.L.M.); and Department of Physiology and Biophysics and Center for Cardiovascular Research, College of Medicine, University of Illinois, Chicago (B.G.P., C.M.W., R.J.S.).
Carl W TongFrom the Department of Medical Physiology (P.C.R., Y.L., M.I.A., B.M.M., C.W.T.) and Division of Molecular Cardiology, Department of Medicine (C.M.T., R.K., K.M.B.), Texas A&M University Health Science Center, College of Medicine, Temple City; Internal Medicine/Division of Cardiology (D.T.K., C.W.T.) and Department of Surgery (G.F.D., D.M.), Baylor Scott & White Health-Central Texas, Temple City; Department of Cell and Regenerative Biology and Biotechnology Center, University of Wisconsin School of Medicine and Public Health, Madison (P.A.P., D.P.F., R.L.M.); and Department of Physiology and Biophysics and Center for Cardiovascular Research, College of Medicine, University of Illinois, Chicago (B.G.P., C.M.W., R.J.S.). CTong@medicine.tamhsc.edu.
Baylor Scott & White Health · USUniversity of Wisconsin–Madison · US
Funding
Sarcomeric Modifications and Progressive Cardiac MaladaptationP01HL062426 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI AI, XUN · 2000 to 2020
$42.4MRYANODINE RECEPTORS, Ca2+-TRIGGERED ARRHYTHMIAS AND HCMP01HL094291 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI MOSS, RICHARD L · 2009 to 2013
$9.7MMy-BP-C Modulation of Cardiac ContractionR37HL082900 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI MOSS, RICHARD L · 2006 to 2015
$6.0MContributions of Cardiac Myosin Binding Protein-C to Healthy and Failing HeartsK08HL114877 · NHLBI · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI TONG, CARL WEI-CHAN · 2012 to 2016
$656kNHLBI NIH HHS K08 HL114877NHLBI NIH HHS K08HL114877NHLBI NIH HHS P01 HL 062426NHLBI NIH HHS P01 HL062426NHLBI NIH HHS P01 HL094291NHLBI NIH HHS R37 HL082900NHLBI NIH HHS R37 HL82900
Abstract
backgroundHeart failure (HF) with preserved ejection fraction (HFpEF) accounts for ≈50% of all cases of HF and currently has no effective treatment. Diastolic dysfunction underlies HFpEF; therefore, elucidation of the mechanisms that mediate relaxation can provide new potential targets for treatment. Cardiac myosin-binding protein-C (cMyBP-C) is a thick filament protein that modulates cross-bridge cycling rates via alterations in its phosphorylation status. Thus, we hypothesize that phosphorylated cMyBP-C accelerates the rate of cross-bridge detachment, thereby enhancing relaxation to mediate diastolic function. METHODS AND
resultsWe compared mouse models expressing phosphorylation-deficient cMyBP-C(S273A/S282A/S302A)-cMyBP-C(t3SA), phosphomimetic cMyBP-C(S273D/S282D/S302D)-cMyBP-C(t3SD), and wild-type-control cMyBP-C(tWT) to elucidate the functional effects of cMyBP-C phosphorylation. Decreased voluntary running distances, increased lung/body weight ratios, and increased brain natriuretic peptide levels in cMyBP-C(t3SA) mice demonstrate that phosphorylation deficiency is associated with signs of HF. Echocardiography (ejection fraction and myocardial relaxation velocity) and pressure/volume measurements (-dP/dtmin, pressure decay time constant τ-Glantz, and passive filling stiffness) show that cMyBP-C phosphorylation enhances myocardial relaxation in cMyBP-C(t3SD) mice, whereas deficient cMyBP-C phosphorylation causes diastolic dysfunction with HFpEF in cMyBP-C(t3SA) mice. Simultaneous force and [Ca(2+)]i measurements on intact papillary muscles show that enhancement of relaxation in cMyBP-C(t3SD) mice and impairment of relaxation in cMyBP-C(t3SA) mice are not because of altered [Ca(2+)]i handling, implicating that altered cross-bridge detachment rates mediate these changes in relaxation rates.
conclusionscMyBP-C phosphorylation enhances relaxation, whereas deficient phosphorylation causes diastolic dysfunction and phenotypes resembling HFpEF. Thus, cMyBP-C is a potential target for treatment of HFpEF.
Indexed as
Ventricular Function, LeftAnimalsBlood PressureCarrier ProteinsCyclic AMP-Dependent Protein KinasesDiastoleGenotypeHeart FailureKineticsMice, TransgenicMutationMyosin Binding Protein CPhenotypePhosphorylationProtein Processing, Post-TranslationalVentricular Dysfunction, LeftCarrier ProteinsCyclic AMP-Dependent Protein KinasesMyosin Binding Protein Cdiastoleheart failuremyocardial contractionmyocardiummyosin-binding protein C
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