TY - JOUR
T1 - Molecular mechanisms of postoperative atrial fibrillation in patients with obstructive sleep apnea
AU - López-Gálvez, Raquel
AU - Rivera-Caravaca, José Miguel
AU - Mandaglio-Collados, Darío
AU - Orenes-Piñero, Esteban
AU - Lahoz, Álvaro
AU - Hernández-Romero, Diana
AU - Martínez, Carlos M.
AU - Carpes, Marina
AU - Arribas, José María
AU - Cánovas, Sergio
AU - Lip, Gregory Y. H.
AU - Marín, Francisco
N1 - © 2023 Federation of American Societies for Experimental Biology.
PY - 2023/6
Y1 - 2023/6
N2 - 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.
AB - 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.
KW - Atrial Fibrillation/complications
KW - Biomarkers
KW - C-Reactive Protein
KW - Fibrosis
KW - Humans
KW - Interleukin-6
KW - MicroRNAs/genetics
KW - Pilot Projects
KW - Prospective Studies
KW - Risk Factors
KW - Sleep Apnea, Obstructive/complications
KW - von Willebrand Factor
KW - obstructive sleep apnea
KW - post-operative atrial fibrillacion
KW - connexins
KW - atrial fibrillation
KW - miRNA
KW - fibrosis
UR - http://www.scopus.com/inward/record.url?scp=85159243177&partnerID=8YFLogxK
U2 - 10.1096/fj.202201965RR
DO - 10.1096/fj.202201965RR
M3 - Journal article
C2 - 37115741
SN - 0892-6638
VL - 37
JO - The FASEB Journal
JF - The FASEB Journal
IS - 6
M1 - e22941
ER -