ArticleThe Journal of clinical investigation2011
Oxidized CaMKII causes cardiac sinus node dysfunction in mice.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers.
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Who cites it
140 citing papers in PubMed.
- HOCPCA Exerts Neuroprotection on Retinal Ganglion Cells by Binding to CaMKIIα and Modulating Oxidative Stress and Neuroinflammation in Experimental Glaucoma.Neuroscience bulletin · 2025Article
- Aging and sinus node dysfunction: mechanisms and future directions.Clinical science (London, England : 1979) · 2025Review
- Metabolic remodelling in atrial fibrillation: manifestations, mechanisms and clinical implications.Nature reviews. Cardiology · 2024Review
- Mechanisms of stretch-induced electro-anatomical remodeling and atrial arrhythmogenesis.Journal of molecular and cellular cardiology · 2024Review
- Proteomics couples electrical remodelling to inflammation in a murine model of heart failure with sinus node dysfunction.Cardiovascular research · 2024Article
- Cardiac monoamine oxidase-A inhibition protects against catecholamine-induced ventricular arrhythmias via enhanced diastolic calcium control.Cardiovascular research · 2024Article
- Administration of USP7 inhibitor p22077 alleviates Angiotensin II (Ang II)-induced atrial fibrillation in Mice.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Article
- Implications for neutrophils in cardiac arrhythmias.American journal of physiology. Heart and circulatory physiology · 2024Review
- Mitochondrial dysfunction is a key link involved in the pathogenesis of sick sinus syndrome: a review.Frontiers in cardiovascular medicine · 2024Review
- Article
- NADPH Oxidases and Oxidative Stress in the Pathogenesis of Atrial Fibrillation.Antioxidants (Basel, Switzerland) · 2023Review
- The Role of Cardiopulmonary Exercise Testing in Hypertrophic Cardiomyopathy.Medicina (Kaunas, Lithuania) · 2023Review
- The role of P21-activated kinase (Pak1) in sinus node function.Journal of molecular and cellular cardiology · 2023Article
- DeepMiceTL: a deep transfer learning based prediction of mice cardiac conduction diseases using early electrocardiograms.Briefings in bioinformatics · 2023Article
- Emergent activity, heterogeneity, and robustness in a calcium feedback model of the sinoatrial node.Biophysical journal · 2023Article
- Characterization of sinoatrial automaticity in Microcebus murinus to study the effect of aging on cardiac activity and the correlation with longevity.Scientific reports · 2023Article
- CaMKII as a Therapeutic Target in Cardiovascular Disease.Annual review of pharmacology and toxicology · 2023Review
- Atrioventricular node dysfunction in pressure overload-induced heart failure-Involvement of the immune system and transcriptomic remodelling.Frontiers in pharmacology · 2023Article
- Genome Editing and Atrial Fibrillation.Advances in experimental medicine and biology · 2023Article
- Hippo-Yap Signaling Maintains Sinoatrial Node Homeostasis.Circulation · 2022Article
80 more citing papers are in PubMed but not listed here.
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22 authors.
Funding
Abstract
Sinus node dysfunction (SND) is a major public health problem that is associated with sudden cardiac death and requires surgical implantation of artificial pacemakers. However, little is known about the molecular and cellular mechanisms that cause SND. Most SND occurs in the setting of heart failure and hypertension, conditions that are marked by elevated circulating angiotensin II (Ang II) and increased oxidant stress. Here, we show that oxidized calmodulin kinase II (ox-CaMKII) is a biomarker for SND in patients and dogs and a disease determinant in mice. In wild-type mice, Ang II infusion caused sinoatrial nodal (SAN) cell oxidation by activating NADPH oxidase, leading to increased ox-CaMKII, SAN cell apoptosis, and SND. p47-/- mice lacking functional NADPH oxidase and mice with myocardial or SAN-targeted CaMKII inhibition were highly resistant to SAN apoptosis and SND, suggesting that ox-CaMKII-triggered SAN cell death contributed to SND. We developed a computational model of the sinoatrial node that showed that a loss of SAN cells below a critical threshold caused SND by preventing normal impulse formation and propagation. These data provide novel molecular and mechanistic information to understand SND and suggest that targeted CaMKII inhibition may be useful for preventing SND in high-risk patients.
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