Circulating Exosomal MicroRNAs and Subclinical Atherosclerosis in Obstructive Sleep Apnea

Sanz-Rubio, David ; Martín-Burriel, Inmaculada (Universidad de Zaragoza) ; Rodríguez, Jorge (Universidad de Zaragoza) ; Marín-Oto, Marta (Universidad de Zaragoza) ; Khalyfa, Abdelnaby ; Sánchez-de-la-Torre, Manuel ; Gozal, David ; Marin, Jose M. (Universidad de Zaragoza)

Resumen: Background. Obstructive sleep apnea (OSA) has been associated with thepathogenesis of atherogenesis. Exosomes and their microRNA (miRNA) cargocould play a major role in this process.Objectives. To determine plasma exosomal miRNA and their relationship withatherosclerosis in patients with OSA.Methods. From the EPIOSA cohort, we selected 50 OSA patients (apnea-hypopnea index–AHI ≥ 10) and 16 age- and sex-matched healthy subjects (AHI≤ 10) for the derivation analysis. The validation assay was composed by 88 OSApatients and 24 matched controls. OSA patients were categorized according toprevalent subclinical atherosclerosis (SA) as defined by ≥ 1 plaque in carotidultrasound. All participants were free of prevalent chronic comorbid conditions.Plasma-derived exosomes were isolated by precipitation, and miRNAs wereevaluated by real-time quantitative PCR.Results. SA was present in 34% of OSA patients. Three exosomal miRNAs wereoverexpressed in patients with OSA and SA at the derivation study: miR-21(relative expression, RE = 2.91), miR-145 (RE = 2.12) and miR-320a (RE =4.06). ROC curve analysis showed a high predictive value for SA of miR-320a(area under curve AUC = 0.813). In the validation cohort, miR-320a alsoexhibited an overexpression of RE = 2.66 among patients with OSA and SA, withan AUC of 0.798. Together with AHI and APO B, miR-320a, was independentlyassociated with SA. In addition, miR-320a correlate with the progression of intimamedia thickness from baseline to after 1 year of follow-up. Finally, miR-320a wasnot reduced after 1 year of follow-up independiently of the treatment with CPAP.3Conclusions. In patients with OSA, exosomal miR-320a is associated to thepresence of subclinical atherosclerosis and could be a useful marker ofcardiovascular risk in these patients

Idioma: Inglés

DOI: 10.1016/j.arbres.2024.12.005

Año: 2024

Publicado en: Archivos de Bronconeumologia
ISSN: 0300-2896

Financiación: info:eu-repo/grantAgreement/ES/DGA/B22-20R
Financiación: info:eu-repo/grantAgreement/ES/DGA-CUS/1466-2020
Financiación: info:eu-repo/grantAgreement/ES/ISCIII CD22-00033
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/PI15-01441
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/PI18-01524
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/PI21-01954
Financiación: info:eu-repo/grantAgreement/ES/MICINN/RYC2019--027831-I

Tipo y forma: Artículo (PostPrint)

Área (Departamento): Área Genética (Dpto. Anatom.,Embri.Genét.Ani.)
Área (Departamento): Area Medicina (Dpto. Medicina, Psiqu. y Derm.)