ArticleCirculation2012
Ca(2+)-stimulated adenylyl cyclase AC1 generates efficient biological pacing as single gene therapy and in combination with HCN2.
Article in Circulation, 2012. 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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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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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
31 citing papers in PubMed, 57 citations in OpenAlex.
- AAV-mediated long-term TBX18 expression causes cardiac fibrosis and fails to induce pacemaker activity in rodents.The Journal of clinical investigation · 2026Article
- Evaluating the prognostic value of systemic immune-inflammatory index in patients with acute decompensated heart failure.ESC heart failure · 2024Article
- Pacemaker Channels and the Chronotropic Response in Health and Disease.Circulation research · 2024Review
- Review
- Cellular and Molecular Mechanisms of Functional Hierarchy of Pacemaker Clusters in the Sinoatrial Node: New Insights into Sick Sinus Syndrome.Journal of cardiovascular development and disease · 2021Review
- Reciprocal interaction between IK1 and If in biological pacemakers: A simulation study.PLoS computational biology · 2021Article
- IPAmerican journal of physiology. Heart and circulatory physiology · 2021Article
- Bioengineering the Cardiac Conduction System: Advances in Cellular, Gene, and Tissue Engineering for Heart Rhythm Regeneration.Frontiers in bioengineering and biotechnology · 2021Review
- Article
- Toward Biological Pacing by Cellular Delivery of Hcn2/SkM1.Frontiers in physiology · 2020Article
- A new combination of transcription factors increases the harvesting efficiency of pacemaker‑like cells.Molecular medicine reports · 2019Article
- Insulin gene enhancer binding protein 1 induces adipose tissue‑derived stem cells to differentiate into pacemaker‑like cells.International journal of molecular medicine · 2019Article
- Cardiomyocyte Progenitor Cells as a Functional Gene Delivery Vehicle for Long-Term Biological Pacing.Molecules (Basel, Switzerland) · 2019Article
- Transcriptional regulation of the cardiac conduction system.Nature reviews. Cardiology · 2018Review
- Direct Reprograming to Regenerate Myocardium and Repair Its Pacemaker and Conduction System.Medicines (Basel, Switzerland) · 2018Review
- Electrophysiological heterogeneity of pacemaker cells in the rabbit intercaval region, including the SA node: insights from recording multiple ion currents in each cell.American journal of physiology. Heart and circulatory physiology · 2018Article
- Current state of the art for cardiac arrhythmia gene therapy.Pharmacology & therapeutics · 2017Review
- Induced Pluripotent Stem Cell-Derived Cardiomyocytes Provide In Vivo Biological Pacemaker Function.Circulation. Arrhythmia and electrophysiology · 2017Article
- Pacing the Heart with Genes: Recent Progress in Biological Pacing.Current cardiology reports · 2015Review
- Gene therapy to restore electrophysiological function in heart failure.Expert opinion on biological therapy · 2015Review
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundBiological pacing performed solely via HCN2 gene transfer in vivo results in relatively slow idioventricular rates and only moderate autonomic responsiveness. We induced biological pacing using the Ca(2+)-stimulated adenylyl cyclase AC1 gene expressed alone or in combination with HCN2 and compared outcomes with those with single-gene HCN2 transfer. METHODS AND
resultsWe implanted adenoviral HCN2, AC1, or HCN2/AC1 constructs into the left bundle branches of atrioventricular-blocked dogs. During steady-state gene expression (days 5-7), differences between AC1, HCN2/AC1, and HCN2 alone were evident in basal beating rate, escape time, and dependence on electronic backup pacing. In HCN2, AC1, and HCN2/AC1, these parameters were as follows: basal beating rate: 50±1.5, 60±5.0, and 129±28.9 bpm (P<0.05 for HCN2/AC1 versus HCN2 or AC1 alone), respectively; escape time: 2.4±0.2, 1.3±0.2, and 1.1±.0.4 seconds (P<0.05 for AC1 and HCN2/AC1 versus HCN2); and percent electronic beats: 34±8%, 2±1%, and 6±2% (P<0.05 for AC1 and HCN2/AC1 versus HCN2). Instantaneous (SD1) and long-term (SD2) heart rate variability and circadian rhythm analyzed via 24-hour Holter recordings showed a shift toward greater sensitivity to parasympathetic modulation in animals injected with AC1 and a high degree of sympathetic modulation in animals injected with HCN2/AC1.
conclusionAC1 or HCN2/AC1 overexpression in left bundle branches provides highly efficient biological pacing and greater sensitivity to autonomic modulation than HCN2 alone.
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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.