000147924 001__ 147924
000147924 005__ 20250109162738.0
000147924 0247_ $$2doi$$a10.3390/ijms242216074
000147924 0248_ $$2sideral$$a141354
000147924 037__ $$aART-2023-141354
000147924 041__ $$aeng
000147924 100__ $$aKhalyfa, Abdelnaby
000147924 245__ $$aMulti-Omics Analysis of Circulating Exosomes in Adherent Long-Term Treated OSA Patients
000147924 260__ $$c2023
000147924 5060_ $$aAccess copy available to the general public$$fUnrestricted
000147924 5203_ $$aObstructive sleep apnea (OSA) is a highly prevalent chronic disease affecting nearly a billion people globally and increasing the risk of multi-organ morbidity and overall mortality. However, the mechanisms underlying such adverse outcomes remain incompletely delineated. Extracellular vesicles (exosomes) are secreted by most cells, are involved in both proximal and long-distance intercellular communication, and contribute toward homeostasis under physiological conditions. A multi-omics integrative assessment of plasma-derived exosomes from adult OSA patients prior to and after 1-year adherent CPAP treatment is lacking. We conducted multi-omic integrative assessments of plasma-derived exosomes from adult OSA patients prior to and following 1-year adherent CPAP treatment to identify potential specific disease candidates. Fasting morning plasma exosomes isolated from 12 adult patients with polysomnographically-diagnosed OSA were analyzed before and after 12 months of adherent CPAP therapy (mean ≥ 6 h/night) (OSAT). Exosomes were characterized by flow cytometry, transmission electron microscopy, and nanoparticle tracking analysis. Endothelial cell barrier integrity, wound healing, and tube formation were also performed. Multi-omics analysis for exosome cargos was integrated. Exosomes derived from OSAT improved endothelial permeability and dysfunction as well as significant improvement in tube formation compared with OSA. Multi-omic approaches for OSA circulating exosomes included lipidomic, proteomic, and small RNA (miRNAs) assessments. We found 30 differentially expressed proteins (DEPs), 72 lipids (DELs), and 13 miRNAs (DEMs). We found that the cholesterol metabolism (has04979) pathway is associated with lipid classes in OSA patients. Among the 12 subjects of OSA and OSAT, seven subjects had complete comprehensive exosome cargo information including lipids, proteins, and miRNAs. Multi-omic approaches identify potential signature biomarkers in plasma exosomes that are responsive to adherent OSA treatment. These differentially expressed molecules may also play a mechanistic role in OSA-induced morbidities and their reversibility. Our data suggest that a multi-omic integrative approach might be useful in understanding how exosomes function, their origin, and their potential clinical relevance, all of which merit future exploration in the context of relevant phenotypic variance. Developing an integrated molecular classification should lead to improved diagnostic classification, risk stratification, and patient management of OSA by assigning molecular disease-specific therapies.
000147924 536__ $$9info:eu-repo/grantAgreement/ES/ISCIII/PI18-01524$$9info:eu-repo/grantAgreement/ES/ISCIII/PI21-01954
000147924 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000147924 590__ $$a4.9$$b2023
000147924 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b66 / 313 = 0.211$$c2023$$dQ1$$eT1
000147924 591__ $$aCHEMISTRY, MULTIDISCIPLINARY$$b68 / 231 = 0.294$$c2023$$dQ2$$eT1
000147924 592__ $$a1.179$$b2023
000147924 593__ $$aMedicine (miscellaneous)$$c2023$$dQ1
000147924 593__ $$aPhysical and Theoretical Chemistry$$c2023$$dQ1
000147924 593__ $$aComputer Science Applications$$c2023$$dQ1
000147924 593__ $$aInorganic Chemistry$$c2023$$dQ1
000147924 593__ $$aSpectroscopy$$c2023$$dQ1
000147924 593__ $$aOrganic Chemistry$$c2023$$dQ1
000147924 593__ $$aMolecular Biology$$c2023$$dQ2
000147924 593__ $$aCatalysis$$c2023$$dQ2
000147924 594__ $$a8.1$$b2023
000147924 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000147924 700__ $$0(orcid)0000-0001-9096-2294$$aMarin, Jose M.$$uUniversidad de Zaragoza
000147924 700__ $$0(orcid)0000-0002-5228-248X$$aSanz-Rubio, David
000147924 700__ $$aLyu, Zhen
000147924 700__ $$aJoshi, Trupti
000147924 700__ $$aGozal, David
000147924 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000147924 773__ $$g24, 22 (2023), 16074 [31 pp.]$$pInt. j. mol. sci.$$tInternational Journal of Molecular Sciences$$x1661-6596
000147924 8564_ $$s8387451$$uhttps://zaguan.unizar.es/record/147924/files/texto_completo.pdf$$yVersión publicada
000147924 8564_ $$s2762863$$uhttps://zaguan.unizar.es/record/147924/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000147924 909CO $$ooai:zaguan.unizar.es:147924$$particulos$$pdriver
000147924 951__ $$a2025-01-09-14:41:56
000147924 980__ $$aARTICLE