Enhanced cardiac CaMKII oxidation and CaMKII-dependent SR Ca leak in patients with sleep-disordered breathing
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...
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| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
8 February 2022
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| In: |
Antioxidants
Year: 2022, Volume: 11, Issue: 2, Pages: 1-15 |
| ISSN: | 2076-3921 |
| DOI: | 10.3390/antiox11020331 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/antiox11020331 Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2076-3921/11/2/331 
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| Author Notes: | Michael Arzt, Marzena A. Drzymalski, Sarah Ripfel, Sebastian Meindl, Alexander Biedermann, Melanie Durczok, Karoline Keller, Julian Mustroph, Sylvia Katz, Maria Tafelmeier, Simon Lebek, Bernhard Flörchinger, Daniele Camboni, Sigrid Wittmann, Johannes Backs, Christof Schmid, Lars S. Maier and Stefan Wagner |
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| 245 | 1 | 0 | |a Enhanced cardiac CaMKII oxidation and CaMKII-dependent SR Ca leak in patients with sleep-disordered breathing |c Michael Arzt, Marzena A. Drzymalski, Sarah Ripfel, Sebastian Meindl, Alexander Biedermann, Melanie Durczok, Karoline Keller, Julian Mustroph, Sylvia Katz, Maria Tafelmeier, Simon Lebek, Bernhard Flörchinger, Daniele Camboni, Sigrid Wittmann, Johannes Backs, Christof Schmid, Lars S. Maier and Stefan Wagner |
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| 520 | |a 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 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). 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. | ||
| 650 | 4 | |a atrial fibrillation | |
| 650 | 4 | |a calcium-calmodulin-dependent protein kinase type II | |
| 650 | 4 | |a sarcoplasmic reticulum Ca leak | |
| 650 | 4 | |a sleep apnea | |
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