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. 2023 Jun;37(6):e22941.
doi: 10.1096/fj.202201965RR.

Molecular mechanisms of postoperative atrial fibrillation in patients with obstructive sleep apnea

Raquel López-Gálvez  1 , José Miguel Rivera-Caravaca  1   2 , Darío Mandaglio-Collados  1 , Esteban Orenes-Piñero  3 , Álvaro Lahoz  4 , Diana Hernández-Romero  5 , Carlos M Martínez  6 , Marina Carpes  6 , José María Arribas  4 , Sergio Cánovas  4 , Gregory Y H Lip  2   7 , Francisco Marín  1
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Molecular mechanisms of postoperative atrial fibrillation in patients with obstructive sleep apnea

Raquel López-Gálvez et al. FASEB J. 2023 Jun.

Abstract

Obstructive sleep apnea (OSA) promotes atrial remodeling and fibrosis, providing a substrate for atrial fibrillation (AF). Herein, we investigate the pathophysiological mechanisms of AF in association with OSA in a cohort of cardiac surgery patients. A prospective study including patients undergoing cardiac surgery. Biomarkers reflective of AF pathophysiology (interleukin [IL-6], C-reactive protein [CRP], von Willebrand factor [vWF], N-terminal pro-brain natriuretic peptide [NT-proBNP], high-sensitivity Troponin T [hs-TnT], and Galectin-3 [Gal-3]) was assessed by functional or immunological assays. miRNAs involved in AF were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Using atrial tissue samples, fibrosis was assessed by Masson's trichrome. Connexin 40 and 43 (Cx40; Cx43) were evaluated by immunolabeling. Fifty-six patients (15 with OSA and 41 non-OSA) were included in this hypothesis-generating pilot study. OSA group had a higher incidence of postoperative AF (POAF) (46.7% vs. 19.5%; p = .042), presented an increased risk of POAF (OR 3.61, 95% CI 1.01-12.92), and had significantly higher baseline levels of NT-proBNP (p = .044), vWF (p = .049), Gal-3 (p = .009), IL-6 (p = .002), and CRP (p = .003). This group presented lower levels of miR-21 and miR-208 (both p < .05). Also, lower Cx40 levels in POAF and/or OSA patients (50.0% vs. 81.8%, p = .033) were found. The presence of interstitial fibrosis (according to myocardial collagen by Masson's trichrome) was raised in OSA patients (86.7% vs. 53.7%, p = .024). Several biomarkers and miRNAs involved in inflammation and fibrosis were dysregulated in OSA patients, which together with a higher degree of interstitial fibrosis, altered miRNA, and Cxs expression predisposes to the development of a substrate that increases the AF risk.

Keywords: atrial fibrillation; connexins; fibrosis; miRNA; obstructive sleep apnea; post-operative atrial fibrillacion.

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References

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