ArticlePLoS computational biology2009
Oxidized calmodulin kinase II regulates conduction following myocardial infarction: a computational analysis.
Article in PLoS computational biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 68 citations in OpenAlex.
- SASP-mediated cellular senescence following myocardial infarction: from spatiotemporal immune regulation to therapeutic strategies.Frontiers in immunology · 2026Review
- Integrative human atrial modelling unravels interactive protein kinase A and Ca2+/calmodulin-dependent protein kinase II signalling as key determinants of atrial arrhythmogenesis.Cardiovascular research · 2023Article
- Hypochlorite-Modified LDL Induces Arrhythmia and Contractile Dysfunction in Cardiomyocytes.Antioxidants (Basel, Switzerland) · 2021Article
- A computational model of pig ventricular cardiomyocyte electrophysiology and calcium handling: Translation from pig to human electrophysiology.PLoS computational biology · 2021Article
- Altered adrenergic response in myocytes bordering a chronic myocardial infarction underlies in vivo triggered activity and repolarization instability.The Journal of physiology · 2020Article
- Role of Oxidation-Dependent CaMKII Activation in the Genesis of Abnormal Action Potentials in Atrial Cardiomyocytes: A Simulation Study.BioMed research international · 2020Article
- A Spatiotemporal Ventricular Myocyte Model Incorporating Mitochondrial Calcium Cycling.Biophysical journal · 2019Article
- βIV-Spectrin/STAT3 complex regulates fibroblast phenotype, fibrosis, and cardiac function.JCI insight · 2019Article
- CaMKII Activity in the Inflammatory Response of Cardiac Diseases.International journal of molecular sciences · 2019Review
- Quantitative systems models illuminate arrhythmia mechanisms in heart failure: Role of the NaWiley interdisciplinary reviews. Systems biology and medicine · 2019Review
- Oxidative stress creates a unique, CaMKII-mediated substrate for atrial fibrillation in heart failure.JCI insight · 2018Article
- Mitochondrial-Mediated Oxidative CaJournal of the American Heart Association · 2018Article
- CaAmerican journal of physiology. Heart and circulatory physiology · 2017Article
- Atrial remodelling in atrial fibrillation: CaMKII as a nodal proarrhythmic signal.Cardiovascular research · 2016Review
- Article
- Cellular and Molecular Mechanisms of Arrhythmia by Oxidative Stress.Cardiology research and practice · 2016Review
- Oxidant stress promotes disease by activating CaMKII.Journal of molecular and cellular cardiology · 2015Review
- Mechanistic Investigation of the Arrhythmogenic Role of Oxidized CaMKII in the Heart.Biophysical journal · 2015Article
- Large Animal Models of Ischemic Cardiomyopathy: Are They Enough to Bridge the Translational Gap?Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology · 2015Article
- Role of CaMKII in cardiac arrhythmias.Trends in cardiovascular medicine · 2015Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Calmodulin kinase II (CaMKII) mediates critical signaling pathways responsible for divergent functions in the heart including calcium cycling, hypertrophy and apoptosis. Dysfunction in the CaMKII signaling pathway occurs in heart disease and is associated with increased susceptibility to life-threatening arrhythmia. Furthermore, CaMKII inhibition prevents cardiac arrhythmia and improves heart function following myocardial infarction. Recently, a novel mechanism for oxidative CaMKII activation was discovered in the heart. Here, we provide the first report of CaMKII oxidation state in a well-validated, large-animal model of heart disease. Specifically, we observe increased levels of oxidized CaMKII in the infarct border zone (BZ). These unexpected new data identify an alternative activation pathway for CaMKII in common cardiovascular disease. To study the role of oxidation-dependent CaMKII activation in creating a pro-arrhythmia substrate following myocardial infarction, we developed a new mathematical model of CaMKII activity including both oxidative and autophosphorylation activation pathways. Computer simulations using a multicellular mathematical model of the cardiac fiber demonstrate that enhanced CaMKII activity in the infarct BZ, due primarily to increased oxidation, is associated with reduced conduction velocity, increased effective refractory period, and increased susceptibility to formation of conduction block at the BZ margin, a prerequisite for reentry. Furthermore, our model predicts that CaMKII inhibition improves conduction and reduces refractoriness in the BZ, thereby reducing vulnerability to conduction block and reentry. These results identify a novel oxidation-dependent pathway for CaMKII activation in the infarct BZ that may be an effective therapeutic target for improving conduction and reducing heterogeneity in the infarcted heart.
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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.