ArticleProceedings of the National Academy of Sciences of the United States of America2013
Transgenic overexpression of ribonucleotide reductase improves cardiac performance.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 46 citations in OpenAlex.
- 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
- Echocardiography to Assess Cardiac Structure and Function in Genetic Cardiomyopathies.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Multiscale computational modeling of the effects of 2'-deoxy-ATP on cardiac muscle calcium handling.Journal of applied physics · 2023Article
- CardiacHeart failure reviews · 2023Review
- dATP elevation induces myocardial metabolic remodeling to support improved cardiac function.Journal of molecular and cellular cardiology · 2023Article
- Structural OFF/ON transitions of myosin in relaxed porcine myocardium predict calcium-activated force.Proceedings of the National Academy of Sciences of the United States of America · 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
- Modulating the tension-time integral of the cardiac twitch prevents dilated cardiomyopathy in murine hearts.JCI insight · 2020Article
- Gene Therapy Rescues Cardiac Dysfunction in Duchenne Muscular Dystrophy Mice by Elevating Cardiomyocyte Deoxy-Adenosine Triphosphate.JACC. Basic to translational science · 2019Article
- p53 prevents doxorubicin cardiotoxicity independently of its prototypical tumor suppressor activities.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Novel Adult-Onset Systolic Cardiomyopathy Due to MYH7 E848G Mutation in Patient-Derived Induced Pluripotent Stem Cells.JACC. Basic to translational science · 2018Article
- Troponin T3 associates with DNA consensus sequence that overlaps with p53 binding motifs.Experimental gerontology · 2018Article
- 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
- Gene therapy for the treatment of heart failure: promise postponed.European heart journal · 2016Review
- AAV6-mediated Cardiac-specific Overexpression of Ribonucleotide Reductase Enhances Myocardial Contractility.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
We previously demonstrated that cardiac myosin can use 2-deoxy-ATP (dATP) as an energy substrate, that it enhances contraction and relaxation with minimal effect on calcium-handling properties in vitro, and that contractile enhancement occurs with only minor elevation of cellular [dATP]. Here, we report the effect of chronically enhanced dATP concentration on cardiac function using a transgenic mouse that overexpresses the enzyme ribonucleotide reductase (TgRR), which catalyzes the rate-limiting step in de novo deoxyribonucleotide biosynthesis. Hearts from TgRR mice had elevated left ventricular systolic function compared with wild-type (WT) mice, both in vivo and in vitro, without signs of hypertrophy or altered diastolic function. Isolated cardiomyocytes from TgRR mice had enhanced contraction and relaxation, with no change in Ca(2+) transients, suggesting targeted improvement of myofilament function. TgRR hearts had normal ATP and only slightly decreased phosphocreatine levels by (31)P NMR spectroscopy, and they maintained rate responsiveness to dobutamine challenge. These data demonstrate long-term (at least 5-mo) elevation of cardiac [dATP] results in sustained elevation of basal left ventricular performance, with maintained β-adrenergic responsiveness and energetic reserves. Combined with results from previous studies, we conclude that this occurs primarily via enhanced myofilament activation and contraction, with similar or faster ability to relax. The data are sufficiently compelling to consider elevated cardiac [dATP] as a therapeutic option to treat systolic dysfunction.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.