000148554 001__ 148554
000148554 005__ 20250120165541.0
000148554 0247_ $$2doi$$a10.1093/sleep/zsz217
000148554 0248_ $$2sideral$$a116903
000148554 037__ $$aART-2020-116903
000148554 041__ $$aeng
000148554 100__ $$aKhalyfa, Abdelnaby
000148554 245__ $$aPlasma exosomes in OSA patients promote endothelial senescence: effect of long-term adherent continuous positive airway pressure
000148554 260__ $$c2020
000148554 5060_ $$aAccess copy available to the general public$$fUnrestricted
000148554 5203_ $$aObstructive sleep apnea (OSA) is associated with increased risk for end-organ morbidities, which can collectively be viewed as accelerated aging. Vascular senescence is an important contributor to end-organ dysfunction. Exosomes are released ubiquitously into the circulation, and transfer their cargo to target cells facilitating physiological and pathological processes. Plasma exosomes from 15 patients with polysomnographically diagnosed OSA at baseline (OSA-T1) after 12 months of adherent continuous positive airway pressure (CPAP) treatment (OSA-T2), 13 untreated OSA patients at 12-month intervals (OSA-NT1, OSA-NT2), and 12 controls (CO1 and CO2) were applied on naïve human microvascular endothelialcells-dermal (HMVEC-d). Expression of several senescence gene markers including p16 (CDKN2A), SIRT1, and SIRT6 and immunostaining for ß-galactosidase activity (x-gal) were performed. Endothelial cells were also exposed to intermittent hypoxia (IH) or normoxia (RA) or treated with hydrogen peroxide (H2O2), stained with x-gal and subjected to qRT-PCR. Exosomes from OSA-T1, OSA-NT1, and OSA-NT2 induced significant increases in x-gal staining compared to OSA-T2, CO1, and CO2 (p-value < 0.01). p16 expression was significantly increased (p < 0.01), while SIRT1 and SIRT6 expression levels were decreased (p < 0.02 and p < 0.009). Endothelial cells exposed to IH or to H2O2 showed significant increases in x-gal staining (p < 0.001) and in senescence gene expression. Circulating exosomes in untreated OSA induce marked and significant increases in senescence of naïve endothelial cells, which are only partially reversible upon long-term adherent CPAP treatment. Furthermore, endothelial cells exposed to IH or H2O2 also elicit similar responses. Thus, OSA either directly or indirectly via exosomes may initiate and exacerbate cellular aging, possibly via oxidative stress-related pathways.
000148554 536__ $$9info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI12-02175$$9info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI15-01940
000148554 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000148554 590__ $$a5.849$$b2020
000148554 591__ $$aNEUROSCIENCES$$b56 / 273 = 0.205$$c2020$$dQ1$$eT1
000148554 591__ $$aCLINICAL NEUROLOGY$$b33 / 208 = 0.159$$c2020$$dQ1$$eT1
000148554 592__ $$a2.222$$b2020
000148554 593__ $$aPhysiology (medical)$$c2020$$dQ1
000148554 593__ $$aNeurology (clinical)$$c2020$$dQ1
000148554 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000148554 700__ $$0(orcid)0000-0001-9096-2294$$aMarín, José M.$$uUniversidad de Zaragoza
000148554 700__ $$aQiao, Zhuanhong
000148554 700__ $$aSanz Rubio, David
000148554 700__ $$aKheirandish-Gozal, Leila
000148554 700__ $$aGozal, David
000148554 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000148554 773__ $$g43, 2 (2020), zsz217 [12 pp.]$$pSleep (N.Y. N.Y.)$$tSleep$$x0161-8105
000148554 85641 $$u10.1093/sleep/zsz217$$zTexto completo de la revista
000148554 8564_ $$s965913$$uhttps://zaguan.unizar.es/record/148554/files/texto_completo.pdf$$yPostprint
000148554 8564_ $$s1956069$$uhttps://zaguan.unizar.es/record/148554/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint
000148554 909CO $$ooai:zaguan.unizar.es:148554$$particulos$$pdriver
000148554 951__ $$a2025-01-20-14:52:59
000148554 980__ $$aARTICLE