ArticleJournal of the American College of Cardiology2013
HCN2/SkM1 gene transfer into canine left bundle branch induces stable, autonomically responsive biological pacing at physiological heart rates.
Article in Journal of the American College of Cardiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 66 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
- The cardiac conduction system: development, function and therapeutic targets.Nature reviews. Cardiology · 2026Review
- Gene therapy for cardiac arrhythmias.Nature reviews. Cardiology · 2026Review
- Gene Therapy for Cardiac Arrhythmias: Mechanisms, Modalities and Therapeutic Applications.Medical sciences (Basel, Switzerland) · 2025Review
- Review
- Gene Therapy for Cardiovascular Disease: Clinical Perspectives.Yonsei medical journal · 2024Review
- Pacemaker Channels and the Chronotropic Response in Health and Disease.Circulation research · 2024Review
- Harnessing cell reprogramming for cardiac biological pacing.Journal of biomedical science · 2023Review
- Conversion of Unmodified Stem Cells to Pacemaker Cells by Overexpression of Key Developmental Genes.Cells · 2023Article
- Enhancement of pacing function by HCN4 overexpression in human pluripotent stem cell-derived cardiomyocytes.Stem cell research & therapy · 2022Article
- Editorial: Cardiac Pacemaking in Health and Disease: From Genes to Function.Frontiers in physiology · 2022Article
- Reciprocal interaction between IK1 and If in biological pacemakers: A simulation study.PLoS computational biology · 2021Article
- Bioengineering the Cardiac Conduction System: Advances in Cellular, Gene, and Tissue Engineering for Heart Rhythm Regeneration.Frontiers in bioengineering and biotechnology · 2021Review
- Biological pacemaker: from biological experiments to computational simulation.Journal of Zhejiang University. Science. B · 2020Review
- Toward Biological Pacing by Cellular Delivery of Hcn2/SkM1.Frontiers in physiology · 2020Article
- 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
- Gene Therapy Approaches to Biological Pacemakers.Journal of cardiovascular development and disease · 2018Review
- 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
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
objectivesThis study sought to test the hypothesis that hyperpolarization-activated cyclic nucleotide-gated (HCN)-based biological pacing might be improved significantly by hyperpolarizing the action potential (AP) threshold via coexpression of the skeletal muscle sodium channel 1 (SkM1).
backgroundGene-based biological pacemakers display effective in vivo pacemaker function. However, approaches used to date have failed to manifest optimal pacemaker properties, defined as basal beating rates of 60 to 90 beats/min, a brisk autonomic response achieving maximal rates of 130 to 160 beats/min, and low to absent electronic backup pacing.
methodsWe implanted adenoviral SkM1, HCN2, or HCN2/SkM1 constructs into left bundle branches (LBB) or left ventricular (LV) epicardium of atrioventricular-blocked dogs.
resultsDuring stable peak gene expression on days 5 to 7, HCN2/SkM1 LBB-injected dogs showed highly stable in vivo pacemaker activity superior to SkM1 or HCN2 alone and superior to LV-implanted dogs with regard to beating rates (resting approximately 80 beats/min; maximum approximately 130 beats/min), no dependence on electronic backup pacing, and enhanced modulation of pacemaker function during circadian rhythm or epinephrine infusion. In vitro isolated LV of dogs overexpressing SkM1 manifested a significantly more negative AP threshold.
conclusionsLBB-injected HCN2/SkM1 potentially provides a more clinically suitable biological pacemaker strategy than other reported constructs. This superiority is attributable to the more negative AP threshold and injection into the LBB.
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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.