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Enhanced Cardiac CaMKII Oxidation and CaMKII-Dependent SR Ca Leak in Patients with Sleep-Disordered Breathing.

ABSTRACT: Sleep-disordered breathing (SDB) is associated with increased oxidant generation. Oxidized Ca/calmodulin kinase II (CaMKII) can contribute to atrial arrhythmias by the stimulation of sarcoplasmic reticulum Ca release events, i.e., Ca sparks. We prospectively enrolled 39 patients undergoing cardiac surgery to screen for SDB and collected right atrial appendage biopsies. SDB was diagnosed in 14 patients (36%). SDB patients had significantly increased levels of oxidized and activated CaMKII (assessed by Western blotting/specific pulldown). Moreover, SDB patients showed a significant increase in Ca spark frequency (CaSpF measured by confocal microscopy) compared with control subjects. CaSpF was 3.58 ± 0.75 (SDB) vs. 2.49 ± 0.84 (no SDB) 1/100 µm-1s-1 (p < 0.05). In linear multivariable regression models, SDB severity was independently associated with increased CaSpF (B [95%CI]: 0.05 [0.03; 0.07], p < 0.001) after adjusting for important comorbidities. Interestingly, 30 min exposure to the CaMKII inhibitor autocamtide-2 related autoinhibitory peptide normalized the increased CaSpF and eliminated the association between SDB and CaSpF (B [95%CI]: 0.01 [-0.1; 0.03], p = 0.387). Patients with SDB have increased CaMKII oxidation/activation and increased CaMKII-dependent CaSpF in the atrial myocardium, independent of major clinical confounders, which may be a novel target for treatment of atrial arrhythmias in SDB.

SUBMITTER: Arzt M

PROVIDER: S-EPMC8868143 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Publications

Enhanced Cardiac CaMKII Oxidation and CaMKII-Dependent SR Ca Leak in Patients with Sleep-Disordered Breathing.

Arzt Michael M Drzymalski Marzena A MA Ripfel Sarah S Meindl Sebastian S Biedermann Alexander A Durczok Melanie M Keller Karoline K Mustroph Julian J Katz Sylvia S Tafelmeier Maria M Lebek Simon S Flörchinger Bernhard B Camboni Daniele D Wittmann Sigrid S Backs Johannes J Schmid Christof C Maier Lars S LS Wagner Stefan S

Antioxidants (Basel, Switzerland) 20220208 2

<h4>Background</h4>Sleep-disordered breathing (SDB) is associated with increased oxidant generation. Oxidized Ca/calmodulin kinase II (CaMKII) can contribute to atrial arrhythmias by the stimulation of sarcoplasmic reticulum Ca release events, i.e., Ca sparks.<h4>Methods</h4>We prospectively enrolled 39 patients undergoing cardiac surgery to screen for SDB and collected right atrial appendage biopsies.<h4>Results</h4>SDB was diagnosed in 14 patients (36%). SDB patients had significantly increase ...[more]

PMID: 35204213

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Project description:ObjectiveTo examine the association between sleep-disordered breathing and stroke outcomes, and determine the contribution of sleep-disordered breathing to outcome disparities in Mexican Americans.MethodsIschemic stroke patients (n = 995), identified from the population-based Brain Attack Surveillance in Corpus Christi Project (2010-2015), were offered participation in a sleep-disordered breathing study including a home sleep apnea test (ApneaLink Plus). Sleep-disordered breathing (respiratory event index ≥10) was determined soon after stroke. Neurologic, functional, cognitive, and quality of life outcomes were assessed at 90 days poststroke. Regression models were used to assess associations between sleep-disordered breathing and outcomes, adjusted for sociodemographics, prestroke function and cognition, health-risk behaviors, stroke severity, and vascular risk factors.ResultsMedian age was 67 years (interquartile range [IQR] = 59-78); 62.1% were Mexican American. Median respiratory event index was 14 (IQR = 6-25); 62.8% had sleep-disordered breathing. Sleep-disordered breathing was associated with worse functional outcome (mean difference in activities of daily living/instrumental activities of daily living score = 0.15, 95% confidence interval [CI] = 0.01-0.28) and cognitive outcome (mean difference in modified Mini-Mental State Examination = -2.66, 95% CI = -4.85 to -0.47) but not neurologic or quality of life outcomes. Sleep-disordered breathing accounted for 9 to 10% of ethnic differences in functional and cognitive outcome and was associated with cognitive outcome more strongly for Mexican Americans (β = -3.97, 95% CI = -6.63 to -1.31) than non-Hispanic whites (β = -0.40, 95% CI = -4.18 to 3.39, p-interaction = 0.15).InterpretationSleep-disordered breathing is associated with worse functional and cognitive function at 90 days poststroke. These outcomes are reasonable endpoints for future trials of sleep-disordered breathing treatment in stroke. If effective, sleep-disordered breathing treatment may somewhat lessen ethnic stroke outcome disparities. ANN NEUROL 2019;86:241-250.

Dataset Information

Enhanced Cardiac CaMKII Oxidation and CaMKII-Dependent SR Ca Leak in Patients with Sleep-Disordered Breathing.

Publications

Enhanced Cardiac CaMKII Oxidation and CaMKII-Dependent SR Ca Leak in Patients with Sleep-Disordered Breathing.

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