ArticleJournal of molecular and cellular cardiology2015
2-Deoxy adenosine triphosphate improves contraction in human end-stage heart failure.
Article in Journal of molecular and cellular cardiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- Molecular mechanisms of altered contraction with the β-myosin R403Q mutation in porcine ventricular muscle and a human stem cell-derived cardiomyocyte model.Journal of molecular and cellular cardiology · 2025Article
- The biochemically defined super relaxed state of myosin-A paradox.The Journal of biological chemistry · 2024Article
- Danicamtiv Increases Myosin Recruitment and Alters Cross-Bridge Cycling in Cardiac Muscle.Circulation research · 2023Article
- dATP elevation induces myocardial metabolic remodeling to support improved cardiac function.Journal of molecular and cellular cardiology · 2023Article
- Human iPSC model reveals a central role for NOX4 and oxidative stress in Duchenne cardiomyopathy.Stem cell reports · 2022Article
- Cardiac myosin contraction and mechanotransduction in health and disease.The Journal of biological chemistry · 2021Review
- Adenosine Deaminase Deficient SCID with Myocardial Hypertrophy.Journal of clinical immunology · 2021Article
- Modulation of post-powerstroke dynamics in myosin II by 2'-deoxy-ADP.Archives of biochemistry and biophysics · 2021Article
- Myosin dynamics during relaxation in mouse soleus muscle and modulation by 2'-deoxy-ATP.The Journal of physiology · 2020Article
- Modulating the tension-time integral of the cardiac twitch prevents dilated cardiomyopathy in murine hearts.JCI insight · 2020Article
- Positional Isomers of a Non-Nucleoside Substrate Differentially Affect Myosin Function.Biophysical journal · 2020Article
- Absence of full-length dystrophin impairs normal maturation and contraction of cardiomyocytes derived from human-induced pluripotent stem cells.Cardiovascular research · 2020Article
- Rapamycin persistently improves cardiac function in aged, male and female mice, even following cessation of treatment.Aging cell · 2020Article
- Defining decreased protein succinylation of failing human cardiac myofibrils in ischemic cardiomyopathy.Journal of molecular and cellular cardiology · 2020Article
- Gene Therapy Rescues Cardiac Dysfunction in Duchenne Muscular Dystrophy Mice by Elevating Cardiomyocyte Deoxy-Adenosine Triphosphate.JACC. Basic to translational science · 2019Article
- Cardiac myosin activation with 2-deoxy-ATP via increased electrostatic interactions with actin.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Fast and sensitive HPLC-MS/MS method for direct quantification of intracellular deoxyribonucleoside triphosphates from tissue and cells.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2017Article
- Molecular mechanisms underlying deoxy-ADP.Pi activation of pre-powerstroke myosin.Protein science : a publication of the Protein Society · 2017Article
- Cardiac Myosin Activation with Gene Therapy Produces Sustained Inotropic Effects and May Treat Heart Failure with Reduced Ejection Fraction.Handbook of experimental pharmacology · 2017Review
- Translation of Cardiac Myosin Activation with 2-deoxy-ATP to Treat Heart Failure via an Experimental Ribonucleotide Reductase-Based Gene Therapy.JACC. Basic to translational science · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
We are developing a novel treatment for heart failure by increasing myocardial 2 deoxy-ATP (dATP). Our studies in rodent models have shown that substitution of dATP for adenosine triphosphate (ATP) as the energy substrate in vitro or elevation of dATP in vivo increases myocardial contraction and that small increases in the native dATP pool of heart muscle are sufficient to improve cardiac function. Here we report, for the first time, the effect of dATP on human adult cardiac muscle contraction. We measured the contractile properties of chemically-demembranated multicellular ventricular wall preparations and isolated myofibrils from human subjects with end-stage heart failure. Isometric force was increased at both saturating and physiologic Ca(2+) concentrations with dATP compared to ATP. This resulted in an increase in the Ca(2+) sensitivity of force (pCa50) by 0.06 pCa units. The rate of force redevelopment (ktr) in demembranated wall muscle was also increased, as was the rate of contractile activation (kACT) in isolated myofibrils, indicating increased cross-bridge binding and cycling compared with ATP in failing human myocardium. These data suggest that dATP could increase dP/dT and end systolic pressure in failing human myocardium. Importantly, even though the magnitude and rate of force development were increased, there was no increase in the time to 50% and 90% myofibril relaxation. These data, along with our previous studies in rodent models, show the promise of elevating myocardial dATP to enhance contraction and restore cardiac pump function. These data also support further pre-clinical evaluation of this new approach for treating heart failure.
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