ArticleJournal of cardiovascular pharmacology2015
Omecamtiv Mecarbil, a Cardiac Myosin Activator, Increases Ca2+ Sensitivity in Myofilaments With a Dilated Cardiomyopathy Mutant Tropomyosin E54K.
Article in Journal of cardiovascular pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 48 citations in OpenAlex.
- Article
- Titin Cardiomyopathy, Emerging Evidence: More Than A Big Heart.Current cardiology reports · 2025Review
- Modulation of striated-muscle contractility by a high-affinity myosin-targeting peptide.Biophysical journal · 2025Article
- Emerging Concepts of Mechanisms Controlling Cardiac Tension: Focus on Familial Dilated Cardiomyopathy (DCM) and Sarcomere-Directed Therapies.Biomedicines · 2024Review
- Assessing Cardiac Contractility From Single Molecules to Whole Hearts.JACC. Basic to translational science · 2024Review
- Mechanism of small molecule inhibition of Plasmodium falciparum myosin A informs antimalarial drug design.Nature communications · 2023Article
- Altered Left Ventricular Rat Gene Expression Induced by the Myosin Activator Omecamtiv Mecarbil.Genes · 2023Article
- Cardiac Sarcomere Signaling in Health and Disease.International journal of molecular sciences · 2022Review
- The Hippo Signaling Pathway as a Drug Target in Familial Dilated Cardiomyopathy.International journal of drug discovery and pharmacology · 2022Article
- Effects of Sarcomere Activators and Inhibitors Targeting Myosin Cross-Bridges on CaMolecular pharmacology · 2022Article
- Effects of omecamtiv mecarbil on the contractile properties of skinned porcine left atrial and ventricular muscles.Frontiers in physiology · 2022Article
- Altered contractility in mutation-specific hypertrophic cardiomyopathy: A mechano-energeticFrontiers in physiology · 2022Article
- Negative inotropic mechanisms of β-cardiotoxin in cardiomyocytes by depression of myofilament ATPase activity without activation of the classical β-adrenergic pathway.Scientific reports · 2021Article
- The clinical utility of pediatric cardiomyopathy genetic testing: From diagnosis to a precision medicine-based approach to care.Progress in pediatric cardiology · 2021Article
- Modulating the tension-time integral of the cardiac twitch prevents dilated cardiomyopathy in murine hearts.JCI insight · 2020Article
- Dilated cardiomyopathy mutations in thin-filament regulatory proteins reduce contractility, suppress systolic CaAmerican journal of physiology. Heart and circulatory physiology · 2020Article
- Energy Cost of Force Production After a Stretch-Shortening Cycle in Skinned Muscle Fibers: Does Muscle Efficiency Increase?Frontiers in physiology · 2020Article
- Myocardial Contractility: Historical and Contemporary Considerations.Frontiers in physiology · 2020Article
- Treatments targeting inotropy.European heart journal · 2019Article
- Dilated cardiomyopathy mutation in the converter domain of human cardiac myosin alters motor activity and response to omecamtiv mecarbil.The Journal of biological chemistry · 2019Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Apart from transplant, there are no satisfactory therapies for the severe depression in contractility in familial dilated cardiomyopathy (DCM). Current heart failure treatments that act by increasing contractility involve signaling cascades that alter calcium homeostasis and induce arrhythmias. Omecamtiv mecarbil is a promising new inotropic agent developed for heart failure that may circumvent such limitations. Omecamtiv is a direct cardiac myosin activator that promotes and prolongs the strong myosin-actin binding conformation to increase the duration of systolic elastance. We tested the effect of omecamtiv on Ca(2+) sensitivity of myofilaments of a DCM mouse model containing a tropomyosin E54K mutation. We compared tension and ATPase activity of detergent-extracted myofilaments with and without treatment with 316 nM omecamtiv at varying pCa values. When transgenic myofilaments were treated with omecamtiv, the pCa50 for activation of tension increased from 5.70 ± 0.02 to 5.82 ± 0.02 and ATPase activity increased from 5.73 ± 0.06 to 6.07 ± 0.04. This significant leftward shift restored Ca(2+) sensitivity to levels no longer significantly different from controls. Proteomic studies lacked changes in sarcomeric protein phosphorylation. Our data demonstrate that omecamtiv can potentially augment cardiac contractility in DCM by increasing Ca(2+) sensitivity. The use of direct myosin activators addresses functional defects without incurring the adverse side effects of Ca(2+)-dependent treatments.
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