ArticleEuropean journal of heart failure2015
Ribonucleotide reductase-mediated increase in dATP improves cardiac performance via myosin activation in a large animal model of heart failure.
Article in European journal of heart failure, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24 citing papers in PubMed, 46 citations in OpenAlex.
- An injectable hydrogen-producing bacteria hydrogel for cardiac repair in rodent and porcine models.Nature biomedical engineering · 2026Article
- A new model of heart failure with preserved ejection fraction induced by metabolic syndrome in Ossabaw miniature swine.Basic research in cardiology · 2025Article
- Intravenous infusions of mesenchymal stromal cells have cumulative beneficial effects in a porcine model of chronic ischaemic cardiomyopathy.Cardiovascular research · 2024Article
- Interacting myosin head dynamics and their modification by 2'-deoxy-ADP.Biophysical journal · 2024Article
- NetSci: A Library for High Performance Biomolecular Simulation Network Analysis Computation.Journal of chemical information and modeling · 2024Article
- Multiscale modeling shows how 2'-deoxy-ATP rescues ventricular function in heart failure.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Multiscale computational modeling of the effects of 2'-deoxy-ATP on cardiac muscle calcium handling.Journal of applied physics · 2023Article
- dATP elevation induces myocardial metabolic remodeling to support improved cardiac function.Journal of molecular and cellular cardiology · 2023Article
- Cardiac myosin contraction and mechanotransduction in health and disease.The Journal of biological chemistry · 2021Review
- Adeno-associated viral (AAV) vector-mediated therapeutics for diabetic cardiomyopathy - current and future perspectives.Clinical science (London, England : 1979) · 2021Review
- Translational research on Myology and Mobility Medicine: 2021 semi-virtual PDM3 from Thermae of Euganean Hills, May 26 - 29, 2021.European journal of translational myology · 2021Article
- Modulation of post-powerstroke dynamics in myosin II by 2'-deoxy-ADP.Archives of biochemistry and biophysics · 2021Article
- 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
- 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
- Controlling load-dependent kinetics of β-cardiac myosin at the single-molecule level.Nature structural & molecular biology · 2018Article
- 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
- Multiparametric CMR imaging of infarct remodeling in a percutaneous reperfused Yucatan mini-pig model.NMR in biomedicine · 2017Article
- Molecular mechanisms underlying deoxy-ADP.Pi activation of pre-powerstroke myosin.Protein science : a publication of the Protein Society · 2017Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
aimsHeart failure remains a leading cause of morbidity, hospitalizations, and deaths. We previously showed that overexpression of the enzyme ribonucleotide reductase (RNR) in cardiomyocytes increased levels of the myosin activator, 2-deoxy-ATP, catalysed enhanced contraction, and improved cardiac performance in rodent hearts. Here we used a swine model of myocardial infarction (MI) to test preliminarily a novel gene therapy for heart failure based on delivery of the human RNR enzyme complex under the control of a cardiac-specific promoter via an adeno-associated virus serotype 6 vector--designated as BB-R12. METHODS AND
resultsWe induced heart failure following MI in Yucatan minipigs by balloon occlusion of the left anterior descending artery. Two weeks, later, pigs received BB-R12 at one of three doses via antegrade coronary infusion. At 2 months post-treatment, LVEF and systolic LV dimension (measured by echocardiography) improved significantly in the high-dose group, despite further deterioration in the saline controls. Haemodynamic parameters including LV end-diastolic pressure, +dP/dt, and -dP/dt all trended towards improvement in the high-dose group. We observed no difference in the histopathological appearance of hearts or other organs from treated animals vs. controls, nor did we encounter any safety or tolerability concerns following BB-R12 delivery.
conclusionThese pilot results suggest cardiac-specific gene therapy using BB-R12 may reverse cardiac dysfunction by myosin activation in a large-animal heart failure model with no observed safety concerns. Thus further research into the therapeutic potential of BB-R12 for patients with chronic heart failure appears warranted.
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