Browsing by Subject "Connexins"

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    Endothelial activation, cell-cell interactions, and inflammatory pathways in postoperative atrial fibrillation following cardiac surgery
    (Elsevier, 2024-11-26) López-Gálvez, Raquel; Rivera Caravaca, José Miguel; Mandaglio-Collados, Darío; Ruiz Alcaraz, Antonio José; Lahoz-Tornos, Álvaro; Hernández Romero, Diana; Orenes-Piñero, Esteban; Ramos-Bratos, María Pilar; Martínez Cáceres, Carlos Manuel; Carpes, Marina; Arribas Leal, José María; Cánovas López, Sergio Juan; Lip, Gregory Y.H.; Marín Ortuño, Francisco; Bioquímica y Biología Molecular B e Inmunología; Facultad de Biología
    Background. Postoperative atrial fibrillation (POAF) is common after cardiac surgery and related to endothelial activation and systemic inflammation. Herein, we investigate the pathophysiological mechanisms of AF through endothelial activation and cell-cell interactions related to the development of POAF. Methods. Patients without previous AF undergoing cardiac surgery were studied. Permanent AF patients were included as positive controls. Interleukin (IL)-6, Von Willebrand factor (vWF), N-terminal pro-brain natriuretic peptide (NT-proBNP), and high sensitivity troponin T (hsTnT) were evaluated by electrochemiluminescence. Vascular cell adhesion molecule-1 (VCAM-1) and human Growth Differentiation Factor 15 (GDF-15) were assessed by ELISA. Connexins (Cxs) 40 and 43 were measured by tissue immunolabelling, and apoptosis by TUNEL assay. Results. We included 117 patients (median age 67: 27.8% female): 17 with permanent AF; 27 with POAF, and 73 with non-AF. Patients with permanent AF and POAF had higher levels of NT-proBNP, hs-TnT, apoptotic nuclei, and decreased Cx43 expression, compared to non-AF patients (all p-value <0.05). VCAM-1 and GDF-15 were significantly higher in permanent AF vs. non-AF (p = 0.013 and p = 0.035). Conclusions. Greater endothelial activation and inflammation in AF patients compared to those without AF were found. The proinflammatory state in AF patients, in addition to the lower expression of Cx43, seems to be associated with atrial remodeling processes occurring in AF.
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    Molecular mechanisms of postoperative atrial fibrillation in patients with obstructive sleep apnea
    (Wiley, 2023-04-28) López Gálvez, Raquel; Rivera Caravaca, José Miguel; Mandaglio Collados, Darío; Lahoz, Álvaro; Carpes, Marina; Arribas, José María; Cánovas López, Sergio; Lip, Gregory Y. H.; Marín, Francisco; Martínez Cáceres, Carlos Manuel; Orenes-Piñero, Esteban; Hernández Romero, Diana; Cirugía, Pediatría y Obstetricia y Ginecología
    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.