Alterations of the Sialylation Machinery in Brugada Syndrome
| Autor: | Andrea Ghiroldi, Giuseppe Ciconte, Pasquale Creo, Adriana Tarantino, Dario Melgari, Sara D’Imperio, Marco Piccoli, Federica Cirillo, Emanuele Micaglio, Michelle M. Monasky, Anthony Frosio, Emanuela T. Locati, Gabriele Vicedomini, Ilaria Rivolta, Carlo Pappone, Luigi Anastasia |
|---|---|
| Přispěvatelé: | Ghiroldi, A, Ciconte, G, Creo, P, Tarantino, A, Melgari, D, D'Imperio, S, Piccoli, M, Cirillo, F, Micaglio, E, Monasky, M, Frosio, A, Locati, E, Vicedomini, G, Rivolta, I, Pappone, C, Anastasia, L |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
glycosylation
PBMC Organic Chemistry General Medicine arrhythmia sudden cardiac death Catalysis NAV1.5 Voltage-Gated Sodium Channel Computer Science Applications Inorganic Chemistry sialylation Electrocardiography Phenotype Brugada Syndrome arrhythmias ventricular tachycardia peripheral cells PBMCs peripheral cell Mutation Leukocytes Mononuclear Humans Physical and Theoretical Chemistry Molecular Biology Spectroscopy |
| Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 21; Pages: 13154 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms232113154 |
| Popis: | Brugada Syndrome (BrS) is an inherited arrhythmogenic disorder with an increased risk of sudden cardiac death. Recent evidence suggests that BrS should be considered as an oligogenic or polygenic condition. Mutations in genes associated with BrS are found in about one-third of patients and they mainly disrupt the cardiac sodium channel NaV1.5, which is considered the main cause of the disease. However, voltage-gated channel’s activity could be impacted by post-translational modifications such as sialylation, but their role in BrS remains unknown. Thus, we analyzed high risk BrS patients (n = 42) and healthy controls (n = 42) to assess an involvement of sialylation in BrS. Significant alterations in gene expression and protein sialylation were detected in Peripheral Blood Mononuclear Cells (PBMCs) from BrS patients. These changes were significantly associated with the phenotypic expression of the disease, as the size of the arrhythmogenic substrate and the duration of epicardial electrical abnormalities. Moreover, protein desialylation caused a reduction in the sodium current in an in vitro NaV1.5-overexpressing model. Dysregulation of the sialylation machinery provides definitive evidence that BrS affects extracardiac tissues, suggesting an underlying cause of the disease. Moreover, detection of these changes at the systemic level and their correlation with the clinical phenotype hint at the existence of a biomarker signature for BrS. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |