ArticleCirculation research2017
Targeting miR-423-5p Reverses Exercise Training-Induced HCN4 Channel Remodeling and Sinus Bradycardia.
Open access · greenAbstract read
In one paragraph
Article in Circulation research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 1 pooled it
8.0field-weighted citation impact, top 2% of its field
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
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.
- The Dual Nature of Sinoatrial Node Remodelling in Athletes: A Systematic Review of Electrophysiological Adaptations and the Pathological Tipping Point.International journal of molecular sciences · 2025Pooled it
- Potential roles of β3-adrenergic receptor in heart rate regulation via sinus node activity and local adipocyte metabolism.The journal of physiological sciences : JPS · 2026Article
- Sports Cardiology in Practice: Exercise as Stressor, Signal, and Therapy.Journal of cardiovascular development and disease · 2026Article
- Platelet-bioengineered hiPSC-sEVs achieve targeted repair of fibrotic sinoatrial node in preclinical SND models.Nature communications · 2025Article
- Sinoatrial Node Dynamics: Clinical Relevance and microRNA-Based Modulation of Pacemaker Activity.Cureus · 2025Review
- The Hidden Regulators: MicroRNAs in Pediatric Heart Development and Disease.Journal of clinical medicine · 2025Review
- Aging and sinus node dysfunction: mechanisms and future directions.Clinical science (London, England : 1979) · 2025Review
- Does Long-Term Sport Practice Facilitate the Development of Idiopathic Bradycardia Requiring Early Pacemaker Implantation During the Course of Life?Journal of cardiovascular development and disease · 2025Article
- Exosomal mir-126-3p derived from endothelial cells induces ion channel dysfunction by targeting RGS3 signaling in cardiomyocytes: a novel mechanism in Takotsubo cardiomyopathy.Stem cell research & therapy · 2025Article
- Extracellular Vesicle-Derived Non-Coding RNAs: Key Mediators in Remodelling Heart Failure.Current issues in molecular biology · 2024Review
- Cardiac conduction diseases: understanding the molecular mechanisms to uncover targets for future treatments.Expert opinion on therapeutic targets · 2024Review
- Sports activities and cardiovascular system change.Physiological research · 2023Review
- miR-423 sponged by lncRNA NORHA inhibits granulosa cell apoptosis.Journal of animal science and biotechnology · 2023Article
- Regulation of Cervical Cancer Development by a Novel Circ_0000212/miR-1236-3p/GREM1 ceRNA Crosstalk.Molecular biotechnology · 2023Article
- MicroRNAs: Midfielders of Cardiac Health, Disease and Treatment.International journal of molecular sciences · 2023Review
- Immediate and sustained increases in the activity of vagal preganglionic neurons during exercise and after exercise training.Cardiovascular research · 2023Article
- Long-Term Training Increases Atrial Fibrillation Sustainability in Standardbred Racehorses.Journal of cardiovascular translational research · 2023Article
- Depressed HCN4 function in the type 2 diabetic sinoatrial node.Molecular and cellular biochemistry · 2023Article
- Emerging Signaling Regulation of Sinoatrial Node Dysfunction.Current cardiology reports · 2023Review
- Non-coding RNA and arrhythmias: expression, function, and molecular mechanism.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2023Review
Corrections and comments
- Commented on by
Authors and funding
25 authors at 4 institutions in 4 countries.
Alicia D'SouzaFrom the Division of Cardiovascular Sciences, University of Manchester, United Kingdom (A.D., C.M.P., Y.W., S.N., S.J.R.J.L., C.C., H.B., Y.Z., J.E., A.R., A.K., E.J.C., O.M., H.D., D.O., G.M.M., M.R.B.); K.G. Jebsen Center for Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway (A.B.J., U.W.); Faculty of Health Sciences, NNF Center for Protein Research, University of Copenhagen, Denmark (N.L., P.C.P., A.L.); School of Healthcare Science, Manchester Metropolitan University, United Kingdom (J.C., J.M.); Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Netherlands (P.A.d.C.M.); and School of Human Movement & Nutrition Sciences, University of Queensland, Australia (U.W.).
Charles M PearmanFrom the Division of Cardiovascular Sciences, University of Manchester, United Kingdom (A.D., C.M.P., Y.W., S.N., S.J.R.J.L., C.C., H.B., Y.Z., J.E., A.R., A.K., E.J.C., O.M., H.D., D.O., G.M.M., M.R.B.); K.G. Jebsen Center for Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway (A.B.J., U.W.); Faculty of Health Sciences, NNF Center for Protein Research, University of Copenhagen, Denmark (N.L., P.C.P., A.L.); School of Healthcare Science, Manchester Metropolitan University, United Kingdom (J.C., J.M.); Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Netherlands (P.A.d.C.M.); and School of Human Movement & Nutrition Sciences, University of Queensland, Australia (U.W.).
Yanwen WangFrom the Division of Cardiovascular Sciences, University of Manchester, United Kingdom (A.D., C.M.P., Y.W., S.N., S.J.R.J.L., C.C., H.B., Y.Z., J.E., A.R., A.K., E.J.C., O.M., H.D., D.O., G.M.M., M.R.B.); K.G. Jebsen Center for Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway (A.B.J., U.W.); Faculty of Health Sciences, NNF Center for Protein Research, University of Copenhagen, Denmark (N.L., P.C.P., A.L.); School of Healthcare Science, Manchester Metropolitan University, United Kingdom (J.C., J.M.); Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Netherlands (P.A.d.C.M.); and School of Human Movement & Nutrition Sciences, University of Queensland, Australia (U.W.).
Shu NakaoFrom the Division of Cardiovascular Sciences, University of Manchester, United Kingdom (A.D., C.M.P., Y.W., S.N., S.J.R.J.L., C.C., H.B., Y.Z., J.E., A.R., A.K., E.J.C., O.M., H.D., D.O., G.M.M., M.R.B.); K.G. Jebsen Center for Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway (A.B.J., U.W.); Faculty of Health Sciences, NNF Center for Protein Research, University of Copenhagen, Denmark (N.L., P.C.P., A.L.); School of Healthcare Science, Manchester Metropolitan University, United Kingdom (J.C., J.M.); Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Netherlands (P.A.d.C.M.); and School of Human Movement & Nutrition Sciences, University of Queensland, Australia (U.W.).
Sunil Jit R J LoganthaFrom the Division of Cardiovascular Sciences, University of Manchester, United Kingdom (A.D., C.M.P., Y.W., S.N., S.J.R.J.L., C.C., H.B., Y.Z., J.E., A.R., A.K., E.J.C., O.M., H.D., D.O., G.M.M., M.R.B.); K.G. Jebsen Center for Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway (A.B.J., U.W.); Faculty of Health Sciences, NNF Center for Protein Research, University of Copenhagen, Denmark (N.L., P.C.P., A.L.); School of Healthcare Science, Manchester Metropolitan University, United Kingdom (J.C., J.M.); Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Netherlands (P.A.d.C.M.); and School of Human Movement & Nutrition Sciences, University of Queensland, Australia (U.W.).
Charlotte CoxFrom the Division of Cardiovascular Sciences, University of Manchester, United Kingdom (A.D., C.M.P., Y.W., S.N., S.J.R.J.L., C.C., H.B., Y.Z., J.E., A.R., A.K., E.J.C., O.M., H.D., D.O., G.M.M., M.R.B.); K.G. Jebsen Center for Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway (A.B.J., U.W.); Faculty of Health Sciences, NNF Center for Protein Research, University of Copenhagen, Denmark (N.L., P.C.P., A.L.); School of Healthcare Science, Manchester Metropolitan University, United Kingdom (J.C., J.M.); Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Netherlands (P.A.d.C.M.); and School of Human Movement & Nutrition Sciences, University of Queensland, Australia (U.W.).
Hayley BennettFrom the Division of Cardiovascular Sciences, University of Manchester, United Kingdom (A.D., C.M.P., Y.W., S.N., S.J.R.J.L., C.C., H.B., Y.Z., J.E., A.R., A.K., E.J.C., O.M., H.D., D.O., G.M.M., M.R.B.); K.G. Jebsen Center for Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway (A.B.J., U.W.); Faculty of Health Sciences, NNF Center for Protein Research, University of Copenhagen, Denmark (N.L., P.C.P., A.L.); School of Healthcare Science, Manchester Metropolitan University, United Kingdom (J.C., J.M.); Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Netherlands (P.A.d.C.M.); and School of Human Movement & Nutrition Sciences, University of Queensland, Australia (U.W.).
Yu ZhangFrom the Division of Cardiovascular Sciences, University of Manchester, United Kingdom (A.D., C.M.P., Y.W., S.N., S.J.R.J.L., C.C., H.B., Y.Z., J.E., A.R., A.K., E.J.C., O.M., H.D., D.O., G.M.M., M.R.B.); K.G. Jebsen Center for Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway (A.B.J., U.W.); Faculty of Health Sciences, NNF Center for Protein Research, University of Copenhagen, Denmark (N.L., P.C.P., A.L.); School of Healthcare Science, Manchester Metropolitan University, United Kingdom (J.C., J.M.); Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Netherlands (P.A.d.C.M.); and School of Human Movement & Nutrition Sciences, University of Queensland, Australia (U.W.).
Anne Berit JohnsenFrom the Division of Cardiovascular Sciences, University of Manchester, United Kingdom (A.D., C.M.P., Y.W., S.N., S.J.R.J.L., C.C., H.B., Y.Z., J.E., A.R., A.K., E.J.C., O.M., H.D., D.O., G.M.M., M.R.B.); K.G. Jebsen Center for Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway (A.B.J., U.W.); Faculty of Health Sciences, NNF Center for Protein Research, University of Copenhagen, Denmark (N.L., P.C.P., A.L.); School of Healthcare Science, Manchester Metropolitan University, United Kingdom (J.C., J.M.); Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Netherlands (P.A.d.C.M.); and School of Human Movement & Nutrition Sciences, University of Queensland, Australia (U.W.).
Nora LinscheidFrom the Division of Cardiovascular Sciences, University of Manchester, United Kingdom (A.D., C.M.P., Y.W., S.N., S.J.R.J.L., C.C., H.B., Y.Z., J.E., A.R., A.K., E.J.C., O.M., H.D., D.O., G.M.M., M.R.B.); K.G. Jebsen Center for Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway (A.B.J., U.W.); Faculty of Health Sciences, NNF Center for Protein Research, University of Copenhagen, Denmark (N.L., P.C.P., A.L.); School of Healthcare Science, Manchester Metropolitan University, United Kingdom (J.C., J.M.); Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Netherlands (P.A.d.C.M.); and School of Human Movement & Nutrition Sciences, University of Queensland, Australia (U.W.).
Pi Camilla PoulsenFrom the Division of Cardiovascular Sciences, University of Manchester, United Kingdom (A.D., C.M.P., Y.W., S.N., S.J.R.J.L., C.C., H.B., Y.Z., J.E., A.R., A.K., E.J.C., O.M., H.D., D.O., G.M.M., M.R.B.); K.G. Jebsen Center for Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway (A.B.J., U.W.); Faculty of Health Sciences, NNF Center for Protein Research, University of Copenhagen, Denmark (N.L., P.C.P., A.L.); School of Healthcare Science, Manchester Metropolitan University, United Kingdom (J.C., J.M.); Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Netherlands (P.A.d.C.M.); and School of Human Movement & Nutrition Sciences, University of Queensland, Australia (U.W.).
Jonathan ElliottFrom the Division of Cardiovascular Sciences, University of Manchester, United Kingdom (A.D., C.M.P., Y.W., S.N., S.J.R.J.L., C.C., H.B., Y.Z., J.E., A.R., A.K., E.J.C., O.M., H.D., D.O., G.M.M., M.R.B.); K.G. Jebsen Center for Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway (A.B.J., U.W.); Faculty of Health Sciences, NNF Center for Protein Research, University of Copenhagen, Denmark (N.L., P.C.P., A.L.); School of Healthcare Science, Manchester Metropolitan University, United Kingdom (J.C., J.M.); Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Netherlands (P.A.d.C.M.); and School of Human Movement & Nutrition Sciences, University of Queensland, Australia (U.W.).
Jessica CoulsonFrom the Division of Cardiovascular Sciences, University of Manchester, United Kingdom (A.D., C.M.P., Y.W., S.N., S.J.R.J.L., C.C., H.B., Y.Z., J.E., A.R., A.K., E.J.C., O.M., H.D., D.O., G.M.M., M.R.B.); K.G. Jebsen Center for Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway (A.B.J., U.W.); Faculty of Health Sciences, NNF Center for Protein Research, University of Copenhagen, Denmark (N.L., P.C.P., A.L.); School of Healthcare Science, Manchester Metropolitan University, United Kingdom (J.C., J.M.); Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Netherlands (P.A.d.C.M.); and School of Human Movement & Nutrition Sciences, University of Queensland, Australia (U.W.).
Jamie McPheeFrom the Division of Cardiovascular Sciences, University of Manchester, United Kingdom (A.D., C.M.P., Y.W., S.N., S.J.R.J.L., C.C., H.B., Y.Z., J.E., A.R., A.K., E.J.C., O.M., H.D., D.O., G.M.M., M.R.B.); K.G. Jebsen Center for Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway (A.B.J., U.W.); Faculty of Health Sciences, NNF Center for Protein Research, University of Copenhagen, Denmark (N.L., P.C.P., A.L.); School of Healthcare Science, Manchester Metropolitan University, United Kingdom (J.C., J.M.); Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Netherlands (P.A.d.C.M.); and School of Human Movement & Nutrition Sciences, University of Queensland, Australia (U.W.).
Abigail RobertsonFrom the Division of Cardiovascular Sciences, University of Manchester, United Kingdom (A.D., C.M.P., Y.W., S.N., S.J.R.J.L., C.C., H.B., Y.Z., J.E., A.R., A.K., E.J.C., O.M., H.D., D.O., G.M.M., M.R.B.); K.G. Jebsen Center for Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway (A.B.J., U.W.); Faculty of Health Sciences, NNF Center for Protein Research, University of Copenhagen, Denmark (N.L., P.C.P., A.L.); School of Healthcare Science, Manchester Metropolitan University, United Kingdom (J.C., J.M.); Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Netherlands (P.A.d.C.M.); and School of Human Movement & Nutrition Sciences, University of Queensland, Australia (U.W.).
Paula A da Costa MartinsFrom the Division of Cardiovascular Sciences, University of Manchester, United Kingdom (A.D., C.M.P., Y.W., S.N., S.J.R.J.L., C.C., H.B., Y.Z., J.E., A.R., A.K., E.J.C., O.M., H.D., D.O., G.M.M., M.R.B.); K.G. Jebsen Center for Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway (A.B.J., U.W.); Faculty of Health Sciences, NNF Center for Protein Research, University of Copenhagen, Denmark (N.L., P.C.P., A.L.); School of Healthcare Science, Manchester Metropolitan University, United Kingdom (J.C., J.M.); Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Netherlands (P.A.d.C.M.); and School of Human Movement & Nutrition Sciences, University of Queensland, Australia (U.W.).
Ashraf KitmittoFrom the Division of Cardiovascular Sciences, University of Manchester, United Kingdom (A.D., C.M.P., Y.W., S.N., S.J.R.J.L., C.C., H.B., Y.Z., J.E., A.R., A.K., E.J.C., O.M., H.D., D.O., G.M.M., M.R.B.); K.G. Jebsen Center for Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway (A.B.J., U.W.); Faculty of Health Sciences, NNF Center for Protein Research, University of Copenhagen, Denmark (N.L., P.C.P., A.L.); School of Healthcare Science, Manchester Metropolitan University, United Kingdom (J.C., J.M.); Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Netherlands (P.A.d.C.M.); and School of Human Movement & Nutrition Sciences, University of Queensland, Australia (U.W.).
Ulrik WisløffFrom the Division of Cardiovascular Sciences, University of Manchester, United Kingdom (A.D., C.M.P., Y.W., S.N., S.J.R.J.L., C.C., H.B., Y.Z., J.E., A.R., A.K., E.J.C., O.M., H.D., D.O., G.M.M., M.R.B.); K.G. Jebsen Center for Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway (A.B.J., U.W.); Faculty of Health Sciences, NNF Center for Protein Research, University of Copenhagen, Denmark (N.L., P.C.P., A.L.); School of Healthcare Science, Manchester Metropolitan University, United Kingdom (J.C., J.M.); Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Netherlands (P.A.d.C.M.); and School of Human Movement & Nutrition Sciences, University of Queensland, Australia (U.W.).
Elizabeth J CartwrightFrom the Division of Cardiovascular Sciences, University of Manchester, United Kingdom (A.D., C.M.P., Y.W., S.N., S.J.R.J.L., C.C., H.B., Y.Z., J.E., A.R., A.K., E.J.C., O.M., H.D., D.O., G.M.M., M.R.B.); K.G. Jebsen Center for Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway (A.B.J., U.W.); Faculty of Health Sciences, NNF Center for Protein Research, University of Copenhagen, Denmark (N.L., P.C.P., A.L.); School of Healthcare Science, Manchester Metropolitan University, United Kingdom (J.C., J.M.); Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Netherlands (P.A.d.C.M.); and School of Human Movement & Nutrition Sciences, University of Queensland, Australia (U.W.).
Oliver MonfrediFrom the Division of Cardiovascular Sciences, University of Manchester, United Kingdom (A.D., C.M.P., Y.W., S.N., S.J.R.J.L., C.C., H.B., Y.Z., J.E., A.R., A.K., E.J.C., O.M., H.D., D.O., G.M.M., M.R.B.); K.G. Jebsen Center for Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway (A.B.J., U.W.); Faculty of Health Sciences, NNF Center for Protein Research, University of Copenhagen, Denmark (N.L., P.C.P., A.L.); School of Healthcare Science, Manchester Metropolitan University, United Kingdom (J.C., J.M.); Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Netherlands (P.A.d.C.M.); and School of Human Movement & Nutrition Sciences, University of Queensland, Australia (U.W.).
Alicia LundbyFrom the Division of Cardiovascular Sciences, University of Manchester, United Kingdom (A.D., C.M.P., Y.W., S.N., S.J.R.J.L., C.C., H.B., Y.Z., J.E., A.R., A.K., E.J.C., O.M., H.D., D.O., G.M.M., M.R.B.); K.G. Jebsen Center for Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway (A.B.J., U.W.); Faculty of Health Sciences, NNF Center for Protein Research, University of Copenhagen, Denmark (N.L., P.C.P., A.L.); School of Healthcare Science, Manchester Metropolitan University, United Kingdom (J.C., J.M.); Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Netherlands (P.A.d.C.M.); and School of Human Movement & Nutrition Sciences, University of Queensland, Australia (U.W.).
Halina DobrzynskiFrom the Division of Cardiovascular Sciences, University of Manchester, United Kingdom (A.D., C.M.P., Y.W., S.N., S.J.R.J.L., C.C., H.B., Y.Z., J.E., A.R., A.K., E.J.C., O.M., H.D., D.O., G.M.M., M.R.B.); K.G. Jebsen Center for Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway (A.B.J., U.W.); Faculty of Health Sciences, NNF Center for Protein Research, University of Copenhagen, Denmark (N.L., P.C.P., A.L.); School of Healthcare Science, Manchester Metropolitan University, United Kingdom (J.C., J.M.); Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Netherlands (P.A.d.C.M.); and School of Human Movement & Nutrition Sciences, University of Queensland, Australia (U.W.).
Delvac OceandyFrom the Division of Cardiovascular Sciences, University of Manchester, United Kingdom (A.D., C.M.P., Y.W., S.N., S.J.R.J.L., C.C., H.B., Y.Z., J.E., A.R., A.K., E.J.C., O.M., H.D., D.O., G.M.M., M.R.B.); K.G. Jebsen Center for Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway (A.B.J., U.W.); Faculty of Health Sciences, NNF Center for Protein Research, University of Copenhagen, Denmark (N.L., P.C.P., A.L.); School of Healthcare Science, Manchester Metropolitan University, United Kingdom (J.C., J.M.); Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Netherlands (P.A.d.C.M.); and School of Human Movement & Nutrition Sciences, University of Queensland, Australia (U.W.).
Gwilym M MorrisFrom the Division of Cardiovascular Sciences, University of Manchester, United Kingdom (A.D., C.M.P., Y.W., S.N., S.J.R.J.L., C.C., H.B., Y.Z., J.E., A.R., A.K., E.J.C., O.M., H.D., D.O., G.M.M., M.R.B.); K.G. Jebsen Center for Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway (A.B.J., U.W.); Faculty of Health Sciences, NNF Center for Protein Research, University of Copenhagen, Denmark (N.L., P.C.P., A.L.); School of Healthcare Science, Manchester Metropolitan University, United Kingdom (J.C., J.M.); Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Netherlands (P.A.d.C.M.); and School of Human Movement & Nutrition Sciences, University of Queensland, Australia (U.W.).
Mark R BoyettFrom the Division of Cardiovascular Sciences, University of Manchester, United Kingdom (A.D., C.M.P., Y.W., S.N., S.J.R.J.L., C.C., H.B., Y.Z., J.E., A.R., A.K., E.J.C., O.M., H.D., D.O., G.M.M., M.R.B.); K.G. Jebsen Center for Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway (A.B.J., U.W.); Faculty of Health Sciences, NNF Center for Protein Research, University of Copenhagen, Denmark (N.L., P.C.P., A.L.); School of Healthcare Science, Manchester Metropolitan University, United Kingdom (J.C., J.M.); Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Netherlands (P.A.d.C.M.); and School of Human Movement & Nutrition Sciences, University of Queensland, Australia (U.W.). mark.boyett@manchester.ac.uk.
Maastricht University · NLManchester Metropolitan University · GBNorwegian University of Science and Technology · NOUniversity of Copenhagen · DK
Funding
British Heart Foundation PG/13/99/30233British Heart Foundation PG/16/77/32400
Abstract
rationaleDownregulation of the pacemaking ion channel, HCN4 (hyperpolarization-activated cyclic nucleotide gated channel 4), and the corresponding ionic current,
objectiveTo test the role of HCN4 in the training-induced bradycardia in human athletes and investigate the role of microRNAs (miRs) in the repression of HCN4. METHODS AND
resultsAs in rodents, the intrinsic heart rate was significantly lower in human athletes than in nonathletes, and in all subjects, the rate-lowering effect of the HCN selective blocker, ivabradine, was significantly correlated with the intrinsic heart rate, consistent with HCN repression in athletes. Next-generation sequencing and quantitative real-time reverse transcription polymerase chain reaction showed remodeling of miRs in the sinus node of swim-trained mice. Computational predictions highlighted a prominent role for miR-423-5p. Interaction between miR-423-5p and HCN4 was confirmed by a dose-dependent reduction in HCN4 3'-untranslated region luciferase reporter activity on cotransfection with precursor miR-423-5p (abolished by mutation of predicted recognition elements). Knockdown of miR-423-5p with anti-miR-423-5p reversed training-induced bradycardia via rescue of HCN4 and
conclusionsHCN remodeling likely occurs in human athletes, as well as in rodent models. miR-423-5p contributes to training-induced bradycardia by targeting HCN4. This work presents the first evidence of miR control of HCN4 and heart rate. miR-423-5p could be a therapeutic target for pathological sinus node dysfunction in veteran athletes.
Indexed as
AdolescentAdultAnimalsBradycardiaExerciseGene Knockdown TechniquesGene TargetingHumansHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsMaleMiceMice, Inbred C57BLMicroRNAsMuscle ProteinsPhysical Conditioning, AnimalPotassium ChannelsHCN4 protein, humanHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsMicroRNAsMIRN423 microRNA, humanMuscle ProteinsPotassium Channelsathletesexercise trainingion channel remodelingmicro-RNAssinoatrial nodesinus bradycardia
Identifiers
What OpenQuestion holds
Textmetadata
LicenceCC BY
Read underepoch 390
Registered trials
None linked
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.