ArticleCirculation research2018
Stress Signaling JNK2 Crosstalk With CaMKII Underlies Enhanced Atrial Arrhythmogenesis.
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In one paragraph
Article in Circulation research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 4 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed, 4 pooled it
6.3field-weighted citation impact, top 3% of its field
What it found
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Who cites it
65 citing papers in PubMed, 4 syntheses or guidelines pooled it, 79 citations in OpenAlex.
- Sacubitril-Valsartan Lowers Atrial Fibrillation Recurrence and Left Atrial Volume Post-catheter Ablation: Systematic Review and Meta-Analysis.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2025Pooled it
- 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.Journal of the American College of Cardiology · 2024Guideline
- Guideline
- Modulated Calcium Homeostasis and Release Events Under Atrial Fibrillation and Its Risk Factors: A Meta-Analysis.Frontiers in cardiovascular medicine · 2021Pooled it
- Role of NADPH oxidase 2-derived reactive oxygen species in cardiac electrophysiological disorders.Channels (Austin, Tex.) · 2026Review
- Understanding the Diseased Atria.Physiology (Bethesda, Md.) · 2026Review
- Exploring the role of CaMKII in exercise-induced cardioprotection.Human cell · 2026Review
- JNK2 Is a Stress Integrator Driving Atrial Fibrillation Pathogenesis in Aging via Gut-Heart Crosstalk.Circulation · 2026Article
- Identification and validation of five hypoxia- and immune-related hub targets in atrial fibrillation.Journal of cardiothoracic surgery · 2026Article
- Differential effects of semaglutide and colchicine on atrial remodeling in rats with reduced ejection fraction after myocardial infarction.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 · 2026Article
- The Interplay Between Periodontitis and Atrial Fibrillation: Inflammation as a Common Pathophysiological Bridge.International journal of molecular sciences · 2026Review
- Signaling pathways regulating VDAC1 overexpression associated with apoptosis, pyroptosis, and ferroptosis.Cell communication and signaling : CCS · 2026Article
- Colchicine in atrial fibrillation: mechanisms, highlights, and current evidence.Frontiers in pharmacology · 2026Review
- Stress-Induced calcium mishandling in cardiac (Patho)physiology.Cellular and molecular life sciences : CMLS · 2025Review
- Acute binge alcohol increases risk of arrhythmias and myocardial fibrosis in a mouse model of arrhythmogenic cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2025Article
- Metabolic Remodeling and Mitochondrial Stress in Atrial Fibrillation: Mechanisms and Translational Targets.Reviews in cardiovascular medicine · 2025Review
- Advances in JNK inhibitor development: therapeutic prospects in neurodegenerative diseases and fibrosis.Archives of pharmacal research · 2025Review
- Atrial Fibrillation in Diabetes: Pathogenesis and Targeted Rhythm Control Strategies.Current issues in molecular biology · 2025Review
- Neuropsychiatry of atrial fibrillation: dementia and beyond.Frontiers in cardiovascular medicine · 2025Review
- Atrial myocyte senescence as a driver of atrial fibrillation: mechanisms and therapeutic implications.Frontiers in cell and developmental biology · 2025Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Jiajie YanFrom the Department of Physiology and Biophysics, Rush University, Chicago, IL (J.Y., W.Z., D.M.D., E.C., M.F., X.A.); Department of Cell and Molecular Physiology (J.Y., W.Z., J.K.T., X.G., D.M.D., E.C., X.W., X.A.) and Department of Thoracic and Cardiovascular Surgery (M.B.), Loyola University Chicago, Maywood, IL; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City (B.C., L.-S.S.); Department of Pharmacology, University of California at Davis (K.S.G., D.M.B.); and Department of Internal Medicine, Johns Hopkins University, Baltimore, MD (M.E.A.).
Weiwei ZhaoFrom the Department of Physiology and Biophysics, Rush University, Chicago, IL (J.Y., W.Z., D.M.D., E.C., M.F., X.A.); Department of Cell and Molecular Physiology (J.Y., W.Z., J.K.T., X.G., D.M.D., E.C., X.W., X.A.) and Department of Thoracic and Cardiovascular Surgery (M.B.), Loyola University Chicago, Maywood, IL; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City (B.C., L.-S.S.); Department of Pharmacology, University of California at Davis (K.S.G., D.M.B.); and Department of Internal Medicine, Johns Hopkins University, Baltimore, MD (M.E.A.).
Justin K ThomsonFrom the Department of Physiology and Biophysics, Rush University, Chicago, IL (J.Y., W.Z., D.M.D., E.C., M.F., X.A.); Department of Cell and Molecular Physiology (J.Y., W.Z., J.K.T., X.G., D.M.D., E.C., X.W., X.A.) and Department of Thoracic and Cardiovascular Surgery (M.B.), Loyola University Chicago, Maywood, IL; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City (B.C., L.-S.S.); Department of Pharmacology, University of California at Davis (K.S.G., D.M.B.); and Department of Internal Medicine, Johns Hopkins University, Baltimore, MD (M.E.A.).
Xianlong GaoFrom the Department of Physiology and Biophysics, Rush University, Chicago, IL (J.Y., W.Z., D.M.D., E.C., M.F., X.A.); Department of Cell and Molecular Physiology (J.Y., W.Z., J.K.T., X.G., D.M.D., E.C., X.W., X.A.) and Department of Thoracic and Cardiovascular Surgery (M.B.), Loyola University Chicago, Maywood, IL; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City (B.C., L.-S.S.); Department of Pharmacology, University of California at Davis (K.S.G., D.M.B.); and Department of Internal Medicine, Johns Hopkins University, Baltimore, MD (M.E.A.).
Dominic M DeMarcoFrom the Department of Physiology and Biophysics, Rush University, Chicago, IL (J.Y., W.Z., D.M.D., E.C., M.F., X.A.); Department of Cell and Molecular Physiology (J.Y., W.Z., J.K.T., X.G., D.M.D., E.C., X.W., X.A.) and Department of Thoracic and Cardiovascular Surgery (M.B.), Loyola University Chicago, Maywood, IL; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City (B.C., L.-S.S.); Department of Pharmacology, University of California at Davis (K.S.G., D.M.B.); and Department of Internal Medicine, Johns Hopkins University, Baltimore, MD (M.E.A.).
Elena CarrilloFrom the Department of Physiology and Biophysics, Rush University, Chicago, IL (J.Y., W.Z., D.M.D., E.C., M.F., X.A.); Department of Cell and Molecular Physiology (J.Y., W.Z., J.K.T., X.G., D.M.D., E.C., X.W., X.A.) and Department of Thoracic and Cardiovascular Surgery (M.B.), Loyola University Chicago, Maywood, IL; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City (B.C., L.-S.S.); Department of Pharmacology, University of California at Davis (K.S.G., D.M.B.); and Department of Internal Medicine, Johns Hopkins University, Baltimore, MD (M.E.A.).
Biyi ChenFrom the Department of Physiology and Biophysics, Rush University, Chicago, IL (J.Y., W.Z., D.M.D., E.C., M.F., X.A.); Department of Cell and Molecular Physiology (J.Y., W.Z., J.K.T., X.G., D.M.D., E.C., X.W., X.A.) and Department of Thoracic and Cardiovascular Surgery (M.B.), Loyola University Chicago, Maywood, IL; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City (B.C., L.-S.S.); Department of Pharmacology, University of California at Davis (K.S.G., D.M.B.); and Department of Internal Medicine, Johns Hopkins University, Baltimore, MD (M.E.A.).
Xiaomin WuFrom the Department of Physiology and Biophysics, Rush University, Chicago, IL (J.Y., W.Z., D.M.D., E.C., M.F., X.A.); Department of Cell and Molecular Physiology (J.Y., W.Z., J.K.T., X.G., D.M.D., E.C., X.W., X.A.) and Department of Thoracic and Cardiovascular Surgery (M.B.), Loyola University Chicago, Maywood, IL; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City (B.C., L.-S.S.); Department of Pharmacology, University of California at Davis (K.S.G., D.M.B.); and Department of Internal Medicine, Johns Hopkins University, Baltimore, MD (M.E.A.).
Kenneth S GinsburgFrom the Department of Physiology and Biophysics, Rush University, Chicago, IL (J.Y., W.Z., D.M.D., E.C., M.F., X.A.); Department of Cell and Molecular Physiology (J.Y., W.Z., J.K.T., X.G., D.M.D., E.C., X.W., X.A.) and Department of Thoracic and Cardiovascular Surgery (M.B.), Loyola University Chicago, Maywood, IL; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City (B.C., L.-S.S.); Department of Pharmacology, University of California at Davis (K.S.G., D.M.B.); and Department of Internal Medicine, Johns Hopkins University, Baltimore, MD (M.E.A.).
Mamdouh BakhosFrom the Department of Physiology and Biophysics, Rush University, Chicago, IL (J.Y., W.Z., D.M.D., E.C., M.F., X.A.); Department of Cell and Molecular Physiology (J.Y., W.Z., J.K.T., X.G., D.M.D., E.C., X.W., X.A.) and Department of Thoracic and Cardiovascular Surgery (M.B.), Loyola University Chicago, Maywood, IL; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City (B.C., L.-S.S.); Department of Pharmacology, University of California at Davis (K.S.G., D.M.B.); and Department of Internal Medicine, Johns Hopkins University, Baltimore, MD (M.E.A.).
Donald M BersFrom the Department of Physiology and Biophysics, Rush University, Chicago, IL (J.Y., W.Z., D.M.D., E.C., M.F., X.A.); Department of Cell and Molecular Physiology (J.Y., W.Z., J.K.T., X.G., D.M.D., E.C., X.W., X.A.) and Department of Thoracic and Cardiovascular Surgery (M.B.), Loyola University Chicago, Maywood, IL; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City (B.C., L.-S.S.); Department of Pharmacology, University of California at Davis (K.S.G., D.M.B.); and Department of Internal Medicine, Johns Hopkins University, Baltimore, MD (M.E.A.).
Mark E AndersonFrom the Department of Physiology and Biophysics, Rush University, Chicago, IL (J.Y., W.Z., D.M.D., E.C., M.F., X.A.); Department of Cell and Molecular Physiology (J.Y., W.Z., J.K.T., X.G., D.M.D., E.C., X.W., X.A.) and Department of Thoracic and Cardiovascular Surgery (M.B.), Loyola University Chicago, Maywood, IL; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City (B.C., L.-S.S.); Department of Pharmacology, University of California at Davis (K.S.G., D.M.B.); and Department of Internal Medicine, Johns Hopkins University, Baltimore, MD (M.E.A.).
Long-Sheng SongFrom the Department of Physiology and Biophysics, Rush University, Chicago, IL (J.Y., W.Z., D.M.D., E.C., M.F., X.A.); Department of Cell and Molecular Physiology (J.Y., W.Z., J.K.T., X.G., D.M.D., E.C., X.W., X.A.) and Department of Thoracic and Cardiovascular Surgery (M.B.), Loyola University Chicago, Maywood, IL; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City (B.C., L.-S.S.); Department of Pharmacology, University of California at Davis (K.S.G., D.M.B.); and Department of Internal Medicine, Johns Hopkins University, Baltimore, MD (M.E.A.).
Michael FillFrom the Department of Physiology and Biophysics, Rush University, Chicago, IL (J.Y., W.Z., D.M.D., E.C., M.F., X.A.); Department of Cell and Molecular Physiology (J.Y., W.Z., J.K.T., X.G., D.M.D., E.C., X.W., X.A.) and Department of Thoracic and Cardiovascular Surgery (M.B.), Loyola University Chicago, Maywood, IL; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City (B.C., L.-S.S.); Department of Pharmacology, University of California at Davis (K.S.G., D.M.B.); and Department of Internal Medicine, Johns Hopkins University, Baltimore, MD (M.E.A.).
Xun AiFrom the Department of Physiology and Biophysics, Rush University, Chicago, IL (J.Y., W.Z., D.M.D., E.C., M.F., X.A.); Department of Cell and Molecular Physiology (J.Y., W.Z., J.K.T., X.G., D.M.D., E.C., X.W., X.A.) and Department of Thoracic and Cardiovascular Surgery (M.B.), Loyola University Chicago, Maywood, IL; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City (B.C., L.-S.S.); Department of Pharmacology, University of California at Davis (K.S.G., D.M.B.); and Department of Internal Medicine, Johns Hopkins University, Baltimore, MD (M.E.A.). xun_ai@rush.edu.
University of Iowa · USUniversity of California, Davis · US
Funding
Sarcomeric Modifications and Progressive Cardiac MaladaptationP01HL062426 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI DE TOMBE, PIETER P. · 2000 to 2020
$42.4MProgram AdministrationP01HL080101 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI BERS, DONALD M · 2006 to 2015
$23.4MPathophysiological Regulation of Cardiac Myocyte RyR ChannelR01HL092097 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Donald M Bers, Robyn T Rebbeck · 2010 to 2026
$9.3MLimiting Pathological Calcium Induced Calcium Release in HeartR01HL057832 · NHLBI · RUSH UNIVERSITY MEDICAL CENTER · PI FILL, MICHAEL, GILLESPIE, DIRK · 1997 to 2024
$9.0MMitochondrial Calmodulin Kinase II in Physiology and DiseaseR01HL070250 · NHLBI · VANDERBILT UNIVERSITY · PI ANDERSON, MARK E · 2002 to 2017
$5.2MThoracic Veins and Sustained Atrial FibrillationR01HL071140 · NHLBI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI CHEN, PENG-SHENG · 2002 to 2014
$4.7MNovel Functions of the E-C Coupling Structural Protein Junctophilin-2 in the HeartR01HL130346 · NHLBI · UNIVERSITY OF IOWA · PI SONG, LONG-SHENG · 2016 to 2023
$4.4MT-tubule remodeling and Ca2+-dependent arrhythmogenesis in cardiomyopathies.R01HL090905 · NHLBI · UNIVERSITY OF IOWA · PI SONG, LONG-SHENG · 2008 to 2017
$4.0MIONIC CONTROL OF CARDIAC MUSCLE CONTRACTION: EC COUPLINGR01HL030077 · NHLBI · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI BERS, DONALD M · 1986 to 2018
$3.8MMulti-scale Systems Model of Murine Heart FailureR01HL105242 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BERS, DONALD M, MCCULLOCH, ANDREW D. · 2012 to 2016
$3.5MMethionine sulfoxide reductase A and oxidized CaMKII in structural heart diseaseR01HL079031 · NHLBI · UNIVERSITY OF IOWA · PI ANDERSON, MARK E · 2006 to 2015
$3.3MThe Stress Response Kinase JNK and Alcohol Evoked Atrial FibrillationR01AA024769 · NIAAA · OHIO STATE UNIVERSITY · PI AI, XUN, CHEN, SUI RONG WAYNE · 2017 to 2021
$3.3MBLRD VA I01 BX002334NHLBI NIH HHS P01 HL062426NHLBI NIH HHS P01 HL080101NHLBI NIH HHS R01 HL030077NHLBI NIH HHS R01 HL057832NHLBI NIH HHS R01 HL070250NHLBI NIH HHS R01 HL071140NHLBI NIH HHS R01 HL079031NHLBI NIH HHS R01 HL090905NHLBI NIH HHS R01 HL092097NHLBI NIH HHS R01 HL096652NHLBI NIH HHS R01 HL105242NHLBI NIH HHS R01 HL113640NHLBI NIH HHS R01 HL130346NHLBI NIH HHS R56 HL071140NIAAA NIH HHS R01 AA024769NIAMS NIH HHS R01 AR054098
Abstract
rationaleAtrial fibrillation (AF) is the most common arrhythmia, and advanced age is an inevitable and predominant AF risk factor. However, the mechanisms that couple aging and AF propensity remain unclear, making targeted therapeutic interventions unattainable.
objectiveTo explore the functional role of an important stress response JNK (c-Jun N-terminal kinase) in sarcoplasmic reticulum Ca METHODS AND
resultsWe used a series of cutting-edge electrophysiological and molecular techniques, exploited the power of transgenic mouse models to detail the molecular mechanism, and verified its clinical applicability in parallel studies on donor human hearts. We discovered that significantly increased activity of the stress response kinase JNK2 (JNK isoform 2) in the aged atria is involved in arrhythmic remodeling. The JNK-driven atrial proarrhythmic mechanism is supported by a pathway linking JNK, CaMKII (Ca
conclusionsWe have identified JNK2-driven CaMKII activation as a novel mode of kinase crosstalk and a causal factor in atrial arrhythmic remodeling, making JNK2 a compelling new therapeutic target for AF prevention and treatment.
Indexed as
AnimalsAtrial FibrillationCalcium-Calmodulin-Dependent Protein Kinase Type 2Calcium SignalingCell LineCells, CulturedHumansMaleMiceMitogen-Activated Protein Kinase 9RabbitsRyanodine Receptor Calcium Release ChannelCalcium-Calmodulin-Dependent Protein Kinase Type 2Mitogen-Activated Protein Kinase 9Ryanodine Receptor Calcium Release Channelagedatrial fibrillationcalcium-calmodulin-dependent protein kinase type 2phosphorylationryanodine receptor 2sarcoplasmic reticulumstress-activated protein kinase JNK2
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