ArticleAmerican journal of physiology. Heart and circulatory physiology2016
2-Deoxyadenosine triphosphate restores the contractile function of cardiac myofibril from adult dogs with naturally occurring dilated cardiomyopathy.
Article in American journal of physiology. Heart and circulatory physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Cardiology's best friend: Using naturally occurring disease in dogs to understand heart disease in humans.Journal of molecular and cellular cardiology plus · 2025Review
- Interacting myosin head dynamics and their modification by 2'-deoxy-ADP.Biophysical journal · 2024Article
- Identification of novel genetic risk factors of dilated cardiomyopathy: from canine to human.Genome medicine · 2023Article
- Predominant myosin superrelaxed state in canine myocardium with naturally occurring dilated cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2023Article
- Danicamtiv Increases Myosin Recruitment and Alters Cross-Bridge Cycling in Cardiac Muscle.Circulation research · 2023Article
- Cardiac myosin contraction and mechanotransduction in health and disease.The Journal of biological chemistry · 2021Review
- Myosin dynamics during relaxation in mouse soleus muscle and modulation by 2'-deoxy-ATP.The Journal of physiology · 2020Article
- Bisphenol S rapidly depresses heart function through estrogen receptor-β and decreases phospholamban phosphorylation in a sex-dependent manner.Scientific reports · 2019Article
- Gene Therapy Rescues Cardiac Dysfunction in Duchenne Muscular Dystrophy Mice by Elevating Cardiomyocyte Deoxy-Adenosine Triphosphate.JACC. Basic to translational science · 2019Article
- New insights provided by myofibril mechanics in inherited cardiomyopathies.Conditioning medicine · 2019Article
- A missense variant in the titin gene in Doberman pinscher dogs with familial dilated cardiomyopathy and sudden cardiac death.Human genetics · 2019Article
- Intracoronary Gene Delivery of the Cytoprotective Factor Vascular Endothelial Growth Factor-BVeterinary sciences · 2019Article
- PI3Kα-regulated gelsolin activity is a critical determinant of cardiac cytoskeletal remodeling and heart disease.Nature communications · 2018Article
- Phenotyping cardiomyopathy in adult zebrafish.Progress in biophysics and molecular biology · 2018Review
- Genetic and Tissue Engineering Approaches to Modeling the Mechanics of Human Heart Failure for Drug Discovery.Frontiers in cardiovascular medicine · 2018Review
- Molecular mechanisms underlying deoxy-ADP.Pi activation of pre-powerstroke myosin.Protein science : a publication of the Protein Society · 2017Article
- Genomic Insights into Cardiomyopathies: A Comparative Cross-Species Review.Veterinary sciences · 2017Review
- 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
- Effects of Cardiac Troponin I Mutation P83S on Contractile Properties and the Modulation by PKA-Mediated Phosphorylation.The journal of physical chemistry. B · 2016Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Dilated cardiomyopathy (DCM) is a major type of heart failure resulting from loss of systolic function. Naturally occurring canine DCM is a widely accepted experimental paradigm for studying human DCM. 2-Deoxyadenosine triphosphate (dATP) can be used by myosin and is a superior energy substrate over ATP for cross-bridge formation and increased systolic function. The objective of this study was to evaluate the beneficial effect of dATP on contractile function of cardiac myofibrils from dogs with naturally occurring DCM. We measured actomyosin NTPase activity and contraction/relaxation properties of isolated myofibrils from nonfailing (NF) and DCM canine hearts. NTPase assays indicated replacement of ATP with dATP significantly increased myofilament activity in both NF and DCM samples. dATP significantly improved maximal tension of DCM myofibrils to the NF sample level. dATP also restored Ca(2+) sensitivity of tension that was reduced in DCM samples. Similarly, dATP increased the kinetics of contractile activation (kACT), with no impact on the rate of cross-bridge tension redevelopment (kTR). Thus, the activation kinetics (kACT/kTR) that were reduced in DCM samples were restored for dATP to NF sample levels. dATP had little effect on relaxation. The rate of early slow-phase relaxation was slightly reduced with dATP, but its duration was not, nor was the fast-phase relaxation or times to 50 and 90% relaxation. Our findings suggest that myosin utilization of dATP improves cardiac myofibril contractile properties of naturally occurring DCM canine samples, restoring them to NF levels, without compromising relaxation. This suggests elevation of cardiac dATP is a promising approach for the treatment of DCM.
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