ArticleCirculation research2016
Constitutive Expression of a Dominant-Negative TGF-β Type II Receptor in the Posterior Left Atrium Leads to Beneficial Remodeling of Atrial Fibrillation Substrate.
Article in Circulation research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed, 55 citations in OpenAlex.
- Article
- Connective tissue disorders and cardiac arrhythmias: genetic pathways, mechanistic bridges, and clinical implications.Frontiers in cardiovascular medicine · 2026Review
- Gene therapy for cardiac arrhythmias.Nature reviews. Cardiology · 2026Review
- Gene Therapies in Atrial Fibrillation.Journal of cardiovascular translational research · 2025Review
- Gene Therapy for Cardiac Arrhythmias: Mechanisms, Modalities and Therapeutic Applications.Medical sciences (Basel, Switzerland) · 2025Review
- Concomitant Diabetes and Atrial Fibrillation: Epicardial Fat and Macrophage-Related Mechanisms.Diabetes/metabolism research and reviews · 2025Review
- Gene therapy for atrial fibrillation.Journal of molecular and cellular cardiology · 2024Review
- Oxidative stress and atrial fibrillation.Journal of molecular and cellular cardiology · 2024Review
- Use of Atrial Fibrillation Electrograms and T1/T2 Magnetic Resonance Imaging to Define the Progressive Nature of Molecular and Structural Remodeling: A New Paradigm Underlying the Emergence of Persistent Atrial Fibrillation.Journal of the American Heart Association · 2024Article
- 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
- Genome Editing and Atrial Fibrillation.Advances in experimental medicine and biology · 2023Article
- Transforming growth factor-β in myocardial disease.Nature reviews. Cardiology · 2022Review
- Left atrial disease and left atrial reverse remodelling across different stages of heart failure development and progression: a new target for prevention and treatment.European journal of heart failure · 2022Review
- A New Hypothetical Concept in Metabolic Understanding of Cardiac Fibrosis: Glycolysis Combined with TGF-β and KLF5 Signaling.International journal of molecular sciences · 2022Review
- Analysis of potential genetic biomarkers using machine learning methods and immune infiltration regulatory mechanisms underlying atrial fibrillation.BMC medical genomics · 2022Article
- Recent advances in gene therapy for atrial fibrillation.Journal of cardiovascular electrophysiology · 2021Review
- Identification of key immune-related genes and immune infiltration in atrial fibrillation with valvular heart disease based on bioinformatics analysis.Journal of thoracic disease · 2021Article
- Article
- Atrial Myopathy Underlying Atrial Fibrillation.Arrhythmia & electrophysiology review · 2020Review
- Enhanced cardiomyocyte reactive oxygen species signaling promotes ibrutinib-induced atrial fibrillation.Redox biology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 1 institution in 1 country.
Funding
Abstract
rationaleFibrosis is an important structural contributor to formation of atrial fibrillation (AF) substrate in heart failure. Transforming growth factor-β (TGF-β) signaling is thought to be intricately involved in creation of atrial fibrosis.
objectiveWe hypothesized that gene-based expression of dominant-negative type II TGF-β receptor (TGF-β-RII-DN) in the posterior left atrium in a canine heart failure model will sufficiently attenuate fibrosis-induced changes in atrial conduction and restitution to decrease AF. Because AF electrograms are thought to reflect AF substrate, we further hypothesized that TGF-β-RII-DN would lead to increased fractionation and decreased organization of AF electrograms. METHODS AND
resultsTwenty-one dogs underwent injection+electroporation in the posterior left atrium of plasmid expressing a dominant-negative TGF-β type II receptor (pUBc-TGFβ-DN-RII; n=9) or control vector (pUBc-LacZ; n=12), followed by 3 to 4 weeks of right ventricular tachypacing (240 bpm). Compared with controls, dogs treated with pUBC-TGFβ-DN-RII demonstrated an attenuated increase in conduction inhomogeneity, flattening of restitution slope and decreased duration of induced AF, with AF electrograms being more fractionated and less organized in pUBc-TGFβ-DN-RII versus pUBc-LacZ dogs. Tissue analysis revealed a significant decrease in replacement/interstitial fibrosis, p-SMAD2/3 and p-ERK1/2.
conclusionsTargeted gene-based reduction of TGF-β signaling in the posterior left atrium-with resulting decrease in replacement fibrosis-led to beneficial remodeling of both conduction and restitution characteristics of the posterior left atrium, translating into a decrease in AF and increased complexity of AF electrograms. In addition to providing mechanistic insights, this data may have important diagnostic and therapeutic implications for AF.
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.