ArticleJCI insight2018
Oxidative stress creates a unique, CaMKII-mediated substrate for atrial fibrillation in heart failure.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 68 citations in OpenAlex.
- Role of NADPH oxidase 2-derived reactive oxygen species in cardiac electrophysiological disorders.Channels (Austin, Tex.) · 2026Review
- Exploring the role of CaMKII in exercise-induced cardioprotection.Human cell · 2026Review
- Modifiable Risk Factors in Atrial Fibrillation: Clinical Implications and Pathophysiological Insights.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2026Review
- NRF2-Targeted Therapy in Cardiovascular Disease Transitions from Systemic Activation to Precision Redox Medicine.Antioxidants (Basel, Switzerland) · 2026Review
- Association of atherogenic index of plasma and triglyceride-glucose index with atrial fibrillation: A retrospective study.PloS one · 2026Article
- Acyl-CoA thioesterase 1 (ACOT1) overexpression alleviates heart failure by inhibiting oxidative stress and cardiomyocyte apoptosis through the Kelch-like ECH-associated protein1-NF-E2-related factor2 (KEAP1-NRF2) pathway.Experimental animals · 2026Article
- Gene Therapies in Atrial Fibrillation.Journal of cardiovascular translational research · 2025Review
- Review
- Administration withCytotechnology · 2025Article
- Macrophage-mediated IL-6 signaling drives ryanodine receptor-2 calcium leak in postoperative atrial fibrillation.The Journal of clinical investigation · 2025Article
- Oxidative stress and atrial fibrillation.Journal of molecular and cellular cardiology · 2024Review
- Aging-associated atrial fibrillation: A comprehensive review focusing on the potential mechanisms.Aging cell · 2024Review
- Mechanisms of stretch-induced electro-anatomical remodeling and atrial arrhythmogenesis.Journal of molecular and cellular cardiology · 2024Review
- The role of iron overload and ferroptosis in arrhythmia pathogenesis.International journal of cardiology. Heart & vasculature · 2024Review
- Focus on the Role of Inflammation as a Bridge between Ferroptosis and Atrial Fibrillation: A Narrative Review and Novel Perspective.Reviews in cardiovascular medicine · 2024Review
- Role of Mitochondrial ROS for Calcium Alternans in Atrial Myocytes.Biomolecules · 2024Article
- Correlation of oxidative stress and vascular endothelial dysfunction with hippocampal perfusion in atrial fibrillation patients with cognitive impairment.SAGE open medicine · 2024Article
- Increased Risk for Atrial Alternans in Rabbit Heart Failure: The Role of CaBiomolecules · 2023Article
- Article
- 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
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
The precise mechanisms by which oxidative stress (OS) causes atrial fibrillation (AF) are not known. Since AF frequently originates in the posterior left atrium (PLA), we hypothesized that OS, via calmodulin-dependent protein kinase II (CaMKII) signaling, creates a fertile substrate in the PLA for triggered activity and reentry. In a canine heart failure (HF) model, OS generation and oxidized-CaMKII-induced (Ox-CaMKII-induced) RyR2 and Nav1.5 signaling were increased preferentially in the PLA (compared with left atrial appendage). Triggered Ca2+ waves (TCWs) in HF PLA myocytes were particularly sensitive to acute ROS inhibition. Computational modeling confirmed a direct relationship between OS/CaMKII signaling and TCW generation. CaMKII phosphorylated Nav1.5 (CaMKII-p-Nav1.5 [S571]) was located preferentially at the intercalated disc (ID), being nearly absent at the lateral membrane. Furthermore, a decrease in ankyrin-G (AnkG) in HF led to patchy dropout of CaMKII-p-Nav1.5 at the ID, causing its distribution to become spatially heterogeneous; this corresponded to preferential slowing and inhomogeneity of conduction noted in the HF PLA. Computational modeling illustrated how conduction slowing (e.g., due to increase in CaMKII-p-Nav1.5) interacts with fibrosis to cause reentry in the PLA. We conclude that OS via CaMKII leads to substrate for triggered activity and reentry in HF PLA by mechanisms independent of but complementary to fibrosis.
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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.