ArticleHeart rhythm2011
Targeted nonviral gene-based inhibition of Gα(i/o)-mediated vagal signaling in the posterior left atrium decreases vagal-induced atrial fibrillation.
Article in Heart rhythm, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 45 citations in OpenAlex.
- Prioritizing Discovery and Advancements in Arrhythmia Therapies: NIH/NHLBI Workshop.JACC. Clinical electrophysiology · 2026Review
- Gene Therapies in Atrial Fibrillation.Journal of cardiovascular translational research · 2025Review
- Autonomic dysregulation and atrial arrhythmias.American journal of physiology. Cell physiology · 2025Review
- Tic-Tac: A Translational Approach in Mechanisms Associated with Irregular Heartbeat and Sinus Rhythm Restoration in Atrial Fibrillation Patients.International journal of molecular sciences · 2023Review
- Atrial fibrillation and sympatho-vagal imbalance: from the choice of the antiarrhythmic treatment to patients with syncope and ganglionated plexi ablation.European heart journal supplements : journal of the European Society of Cardiology · 2023Article
- Research Opportunities in Autonomic Neural Mechanisms of Cardiopulmonary Regulation: A Report From the National Heart, Lung, and Blood Institute and the National Institutes of Health Office of the Director Workshop.JACC. Basic to translational science · 2022Review
- Recent advances in gene therapy for atrial fibrillation.Journal of cardiovascular electrophysiology · 2021Review
- Atrial fibrillation and autonomic nervous system: A translational approach to guide therapeutic goals.Journal of arrhythmia · 2021Review
- Autonomic Dysfunction and Neurohormonal Disorders in Atrial Fibrillation.Cardiac electrophysiology clinics · 2021Review
- Article
- Gene therapy for atrial fibrillation - How close to clinical implementation?International journal of cardiology · 2019Review
- Autonomic Nervous System Dysfunction: JACC Focus Seminar.Journal of the American College of Cardiology · 2019Review
- Acetylcholine Delays Atrial Activation to Facilitate Atrial Fibrillation.Frontiers in physiology · 2019Article
- Gene Therapy for the Treatment of Cardiac Arrhythmias: Current and Emerging Applications.The Journal of innovations in cardiac rhythm management · 2018Review
- Oxidative stress creates a unique, CaMKII-mediated substrate for atrial fibrillation in heart failure.JCI insight · 2018Article
- Gene Therapy Approaches to Biological Pacemakers.Journal of cardiovascular development and disease · 2018Review
- Clinical Effects of "Selective Drug" Regulating Vagus Nerve Signal Pathway in Vagally-Mediated Atrial Fibrillation.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Gene Therapy for Atrial Fibrillation in Heart Failure.Clinical pharmacology and therapeutics · 2017Review
- Improving Atrial Fibrillation Therapy: Is There a Gene for That?Journal of the American College of Cardiology · 2017Review
- Constitutive Expression of a Dominant-Negative TGF-β Type II Receptor in the Posterior Left Atrium Leads to Beneficial Remodeling of Atrial Fibrillation Substrate.Circulation research · 2016Article
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPharmacologic and ablative therapies for atrial fibrillation (AF) have suboptimal efficacy. Newer gene-based approaches that target specific mechanisms underlying AF are likely to be more efficacious in treating AF. Parasympathetic signaling appears to be an important contributor to AF substrate.
objectiveThe purpose of this study was to develop a nonviral gene-based strategy to selectively inhibit vagal signaling in the left atrium and thereby suppress vagal-induced AF.
methodsIn eight dogs, plasmid DNA vectors (minigenes) expressing Gα(i) C-terminal peptide (Gα(i)ctp) was injected in the posterior left atrium either alone or in combination with minigene expressing Gα(o)ctp, followed by electroporation. In five control dogs, minigene expressing scrambled peptide (Gα(R)ctp) was injected. Vagal- and carbachol-induced left atrial effective refractory periods (ERPs), AF inducibility, and Gα(i/o)ctp expression were assessed 3 days following minigene delivery.
resultsVagal stimulation- and carbachol-induced effective refractory period shortening and AF inducibility were significantly attenuated in atria receiving a Gα(i2)ctp-expressing minigene and were nearly eliminated in atria receiving both Gα(i2)ctp- and Gα(o1)ctp-expressing minigenes.
conclusionInhibition of both G(i) and G(o) proteins is necessary to abrogate vagal-induced AF in the left atrium and can be achieved via constitutive expression of Gα(i/o)ctps expressed by nonviral plasmid vectors delivered to the posterior left atrium.
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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.