ArticleCirculation2009
Long-term cardiac-targeted RNA interference for the treatment of heart failure restores cardiac function and reduces pathological hypertrophy.
Article in Circulation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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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.
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Who cites it
105 citing papers in PubMed, 216 citations in OpenAlex.
- RNA-Based Therapies for Treating Monogenic Cardiomyopathies.The Canadian journal of cardiology · 2026Review
- Intravenous rAAV9 Produces Time-Resolved Parenchymal Labeling Downstream of the Vasculature in Adult Mice.Biology · 2026Article
- Cardioprotective role of RBFox1 in myocardial infarction-induced heart failure.Cardiovascular research · 2025Article
- Targeting Calcium Regulation for Heart Failure and Arrhythmia Therapeutics: A Critical Review.Circulation · 2025Review
- Review
- The promise of RNA-based therapeutics in revolutionizing heart failure management - a narrative review of current evidence.Annals of medicine and surgery (2012) · 2023Review
- Phospholamban pentamerization increases sensitivity and dynamic range of cardiac relaxation.Cardiovascular research · 2023Article
- Innate Immunity in Cardiovascular Diseases-Identification of Novel Molecular Players and Targets.Journal of clinical medicine · 2023Review
- tRNA-like Transcripts from theCells · 2022Article
- Research Advances of Injectable Functional Hydrogel Materials in the Treatment of Myocardial Infarction.Gels (Basel, Switzerland) · 2022Review
- Highly Selective SERCA2a Activators: Preclinical Development of a Congeneric Group of First-in-Class Drug Leads against Heart Failure.Journal of medicinal chemistry · 2022Article
- SERCA2a stimulation by istaroxime improves intracellular Ca2+ handling and diastolic dysfunction in a model of diabetic cardiomyopathy.Cardiovascular research · 2022Article
- Transient Post-Natal Exposure to Xenoestrogens Induces Long-Term Alterations in Cardiac Calcium Signaling.Toxics · 2022Article
- Emerging roles of circRNAs in the pathological process of myocardial infarction.Molecular therapy. Nucleic acids · 2021Review
- Cardiovascular consequences of viral infections: from COVID to other viral diseases.Cardiovascular research · 2021Review
- Delivery of transcription factors as modulators of cell differentiation.Drug delivery and translational research · 2021Review
- FGF13 Is a Novel Regulator of NF-κB and Potentiates Pathological Cardiac Hypertrophy.iScience · 2020Article
- XPO1 Gene Therapy Attenuates Cardiac Dysfunction in Rats with Chronic Induced Myocardial Infarction.Journal of cardiovascular translational research · 2020Article
- Targeting senescent cells to attenuate cardiovascular disease progression.Ageing research reviews · 2020Review
- Genetic ablation of Cullin-RING E3 ubiquitin ligase 7 restrains pressure overload-induced myocardial fibrosis.PloS one · 2020Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
24 authors at 1 institution in 1 country.
Funding
Abstract
backgroundRNA interference (RNAi) has the potential to be a novel therapeutic strategy in diverse areas of medicine. Here, we report on targeted RNAi for the treatment of heart failure, an important disorder in humans that results from multiple causes. Successful treatment of heart failure is demonstrated in a rat model of transaortic banding by RNAi targeting of phospholamban, a key regulator of cardiac Ca(2+) homeostasis. Whereas gene therapy rests on recombinant protein expression as its basic principle, RNAi therapy uses regulatory RNAs to achieve its effect. METHODS AND
resultsWe describe structural requirements to obtain high RNAi activity from adenoviral and adeno-associated virus (AAV9) vectors and show that an adenoviral short hairpin RNA vector (AdV-shRNA) silenced phospholamban in cardiomyocytes (primary neonatal rat cardiomyocytes) and improved hemodynamics in heart-failure rats 1 month after aortic root injection. For simplified long-term therapy, we developed a dimeric cardiotropic adeno-associated virus vector (rAAV9-shPLB) to deliver RNAi activity to the heart via intravenous injection. Cardiac phospholamban protein was reduced to 25%, and suppression of sacroplasmic reticulum Ca(2+) ATPase in the HF groups was rescued. In contrast to traditional vectors, rAAV9 showed high affinity for myocardium but low affinity for liver and other organs. rAAV9-shPLB therapy restored diastolic (left ventricular end-diastolic pressure, dp/dt(min), and tau) and systolic (fractional shortening) functional parameters to normal ranges. The massive cardiac dilation was normalized, and cardiac hypertrophy, cardiomyocyte diameter, and cardiac fibrosis were reduced significantly. Importantly, no evidence was found of microRNA deregulation or hepatotoxicity during these RNAi therapies.
conclusionsOur data show for the first time the high efficacy of an RNAi therapeutic strategy in a cardiac disease.
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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.