ArticleMolecular therapy : the journal of the American Society of Gene Therapy2016
AAV6-mediated Cardiac-specific Overexpression of Ribonucleotide Reductase Enhances Myocardial Contractility.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 41 citations in OpenAlex.
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- 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
- Targeted CRISPR activation is functional in engineered human pluripotent stem cells but undergoes silencing after differentiation into cardiomyocytes and endothelium.Cellular and molecular life sciences : CMLS · 2024Article
- Echocardiography to Assess Cardiac Structure and Function in Genetic Cardiomyopathies.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Article
- 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
- Identification of Hub Genes in the Remodeling of Non-Infarcted Myocardium Following Acute Myocardial Infarction.Journal of cardiovascular development and disease · 2022Article
- RRM2 Alleviates Doxorubicin-Induced Cardiotoxicity through the AKT/mTOR Signaling Pathway.Biomolecules · 2022Article
- Human iPSC model reveals a central role for NOX4 and oxidative stress in Duchenne cardiomyopathy.Stem cell reports · 2022Article
- Identification of cardiomyopathy-related core genes through human metabolic networks and expression data.BMC genomics · 2022Article
- Identification and validation of the miRNA-mRNA regulatory network in fetoplacental arterial endothelial cells of gestational diabetes mellitus.Bioengineered · 2021Article
- 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
- RRM2 Improves Cardiomyocyte Proliferation after Myocardial Ischemia Reperfusion Injury through the Hippo-YAP Pathway.Disease markers · 2021Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Impaired systolic function, resulting from acute injury or congenital defects, leads to cardiac complications and heart failure. Current therapies slow disease progression but do not rescue cardiac function. We previously reported that elevating the cellular 2 deoxy-ATP (dATP) pool in transgenic mice via increased expression of ribonucleotide reductase (RNR), the enzyme that catalyzes deoxy-nucleotide production, increases myosin-actin interaction and enhances cardiac muscle contractility. For the current studies, we initially injected wild-type mice retro-orbitally with a mixture of adeno-associated virus serotype-6 (rAAV6) containing a miniaturized cardiac-specific regulatory cassette (cTnT(455)) composed of enhancer and promotor portions of the human cardiac troponin T gene (TNNT2) ligated to rat cDNAs encoding either the Rrm1 or Rrm2 subunit. Subsequent studies optimized the system by creating a tandem human RRM1-RRM2 cDNA with a P2A self-cleaving peptide site between the subunits. Both rat and human Rrm1/Rrm2 cDNAs resulted in RNR enzyme overexpression exclusively in the heart and led to a significant elevation of left ventricular (LV) function in normal mice and infarcted rats, measured by echocardiography or isolated heart perfusions, without adverse cardiac remodeling. Our study suggests that increasing RNR levels via rAAV-mediated cardiac-specific expression provide a novel gene therapy approach to potentially enhance cardiac systolic function in animal models and patients with heart failure.
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