ArticleJournal of the American College of Cardiology2017
Protein Phosphatase Inhibitor-1 Gene Therapy in a Swine Model of Nonischemic Heart Failure.
Article in Journal of the American College of Cardiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Progress in the treatment of diabetic cardiomyopathy, a systematic review.Pharmacology research & perspectives · 2024Pooled it
- Past, Present and Future of Regenerative Gene Therapy for Ischemic Heart Failure.Journal of cardiovascular translational research · 2026Review
- Smoking behaviour, altered DNA methylation, and heart failure risk: evidence from a prospective cohort and epigenetic Mendelian randomization study.Clinical epigenetics · 2026Article
- Cardiac gene therapy makes a comeback.Nature medicine · 2025Article
- Cardiotropic AAV gene therapy for heart failure: a phase 1 trial.Nature medicine · 2025Article
- Gene therapy in cardiac and vascular diseases: a review of approaches to treat genetic and common cardiovascular diseases with novel gene-based therapeutics.Cardiovascular research · 2025Review
- The calcium awakens: new insights in cardiac gene therapy.Frontiers in endocrinology · 2025Article
- Barriers in Heart Failure Gene Therapy and Approaches to Overcome Them.Heart, lung & circulation · 2023Article
- Experimental heart failure models in small animals.Heart failure reviews · 2023Review
- Targeting calcium regulators as therapy for heart failure: focus on the sarcoplasmic reticulum Ca-ATPase pump.Frontiers in cardiovascular medicine · 2023Review
- Recent Advances in Gene Therapy for Cardiac Tissue Regeneration.International journal of molecular sciences · 2021Review
- Adeno-associated viral (AAV) vector-mediated therapeutics for diabetic cardiomyopathy - current and future perspectives.Clinical science (London, England : 1979) · 2021Review
- Cardiac T-Tubule cBIN1-Microdomain, a Diagnostic Marker and Therapeutic Target of Heart Failure.International journal of molecular sciences · 2021Review
- The Neonatal and Juvenile Pig in Pediatric Drug Discovery and Development.Pharmaceutics · 2020Review
- Echocardiographic Left Ventricular Mass Estimation: Two-Dimensional Area-Length Method is Superior to M-Mode Linear Method in Swine Models of Cardiac Diseases.Journal of cardiovascular translational research · 2020Article
- Strategies for targeting the cardiac sarcomere: avenues for novel drug discovery.Expert opinion on drug discovery · 2020Review
- Pathophysiology of Calcium Mediated Ventricular Arrhythmias and Novel Therapeutic Options with Focus on Gene Therapy.International journal of molecular sciences · 2019Review
- Experimental models of cardiac physiology and pathology.Heart failure reviews · 2019Review
- Inhibitor 1 of Protein Phosphatase 1 Regulates CaOxidative medicine and cellular longevity · 2019Article
- Angiogenic Endothelial Cell Signaling in Cardiac Hypertrophy and Heart Failure.Frontiers in cardiovascular medicine · 2019Review
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Authors and funding
19 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundIncreased protein phosphatase-1 in heart failure (HF) induces molecular changes deleterious to the cardiac cell. Inhibiting protein phosphatase-1 through the overexpression of a constitutively active inhibitor-1 (I-1c) has been shown to reverse cardiac dysfunction in a model of ischemic HF.
objectivesThis study sought to determine the therapeutic efficacy of a re-engineered adenoassociated viral vector carrying I-1c (BNP116.I-1c) in a preclinical model of nonischemic HF, and to assess thoroughly the safety of BNP116.I-1c gene therapy.
methodsVolume-overload HF was created in Yorkshire swine by inducing severe mitral regurgitation. One month after mitral regurgitation induction, pigs were randomized to intracoronary delivery of either BNP116.I-1c (n = 6) or saline (n = 7). Therapeutic efficacy and safety were evaluated 2 months after gene delivery. Additionally, 24 naive pigs received different doses of BNP116.I-1c for safety evaluation.
resultsAt 1 month after mitral regurgitation induction, pigs developed HF as evidenced by increased left ventricular end-diastolic pressure and left ventricular volume indexes. Treatment with BNP116.I-1c resulted in improved left ventricular ejection fraction (-5.9 ± 4.2% vs. 5.5 ± 4.0%; p < 0.001) and adjusted dP/dt maximum (-3.39 ± 2.44 s
conclusionsIntracoronary delivery of BNP116.I-1c was safe and improved contractility of the left ventricle and atrium in a large animal model of nonischemic HF.
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