Arzt, Michael and Drzymalski, Marzena A. and Ripfel, Sarah and Meindl, Sebastian and Biedermann, Alexander and Durczok, Melanie and Keller, Karoline and Mustroph, Julian and Katz, Sylvia and Tafelmeier, Maria and Lebek, Simon and Floerchinger, Bernhard and Camboni, Daniele and Wittmann, Sigrid and Backs, Johannes and Schmid, Christof and Maier, Lars S. and Wagner, Stefan (2022) Enhanced Cardiac CaMKII Oxidation and CaMKII-Dependent SR Ca Leak in Patients with Sleep-Disordered Breathing. ANTIOXIDANTS, 11 (2): 331. ISSN , 2076-3921
Full text not available from this repository. (Request a copy)Abstract
Background: 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. Methods: We prospectively enrolled 39 patients undergoing cardiac surgery to screen for SDB and collected right atrial appendage biopsies. Results: 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 mu m(-1)s(-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). Conclusions: 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PROTEIN-KINASE-II; POSITIVE AIRWAY PRESSURE; ATRIAL-FIBRILLATION; CARDIOVASCULAR-DISEASE; HEART-FAILURE; APNEA; ASSOCIATION; ACTIVATION; STROKE; RISK; calcium-calmodulin-dependent protein kinase type II; sleep apnea; atrial fibrillation; sarcoplasmic reticulum Ca leak |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Anästhesiologie Medicine > Lehrstuhl für Herz-, Thorax- und herznahe Gefäßchirurgie Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Dec 2023 15:27 |
| Last Modified: | 05 Dec 2023 15:27 |
| URI: | https://pred.uni-regensburg.de/id/eprint/56965 |
Actions (login required)
 |
View Item |
