000136286 001__ 136286
000136286 005__ 20240731105611.0
000136286 0247_ $$2doi$$a10.1002/jcsm.13539
000136286 0248_ $$2sideral$$a139312
000136286 037__ $$aART-2024-139312
000136286 041__ $$aeng
000136286 100__ $$0(orcid)0000-0001-5612-0253$$aAparicio, Paula$$uUniversidad de Zaragoza
000136286 245__ $$aProteomic profiling of human plasma extracellular vesicles identifies PF4 and C1R as novel biomarker in sarcopenia
000136286 260__ $$c2024
000136286 5060_ $$aAccess copy available to the general public$$fUnrestricted
000136286 5203_ $$aBackground: Sarcopenia, the gradual and generalized loss of muscle mass and function with ageing, is one of the major health problems in older adults, given its high prevalence and substantial socioeconomic implications. Despite the extensive efforts to reach consensus on definition and diagnostic tests and cut‐offs for sarcopenia, there is an urgent and unmet need for non‐invasive, specific and sensitive biomarkers for the disease. Extracellular vesicles (EVs) are present in different biofluids including plasma, whose cargo reflects cellular physiology. This work analysed EV proteome in sarcopenia and robust patients in the search for differentially contained proteins that can be used to diagnose the disease. Methods: Plasma small EVs (sEVs) from a total of 29 robust controls (aged 73.4 ± 5.6 years; 11 men and 18 women) and 49 sarcopenic patients (aged 82.3 ± 5.4 years; 15 men and 34 women) aged 65 years and older were isolated and their cargo was analysed by proteomics. Proteins whose concentration in sEVs was different between sarcopenic and robust patients were further validated using ELISA. The concentration of these candidates was correlated to the EWGSOP2 sarcopenia tests for low muscle strength and low physical performance, and receiver operating characteristic (ROC) curve analyses were carried out to evaluate their diagnostic power, sensitivity and specificity. Results: Proteomic analysis identified 157 sEVs proteins in both sarcopenic and robust samples. Among them, 48 proteins had never been reported in the ExoCarta nor Vesiclepedia databases. Statistical analysis revealed eight proteins whose concentration was significantly different between groups: PF4 (log2 FC = 4.806), OIT3 (log2 FC = −1.161), MMRN1 (log2 FC = −1.982), MASP1 (log2 FC = −0.627), C1R (log2 FC = 1.830), SVEP1 (log2 FC = 1.295), VCAN (FC = 0.937) and SPTB (log2 FC = 1.243). Among them, platelet factor 4 (PF4) showed the lowest concentration while Complement C1r subcomponent (C1R) increased the most in sarcopenic patients, being these results confirmed by ELISA (P = 1.07E‐09 and P = 0.001287, respectively). The concentrations of candidate proteins significantly correlated with EWGSOP2 tests currently used. ROC curve analysis showed an area under the curve of 0.8921 and 0.7476 for PF4 and C1R, respectively. Choosing the optimal for PF4, 80% sensitivity and 85.71% specificity was reached while the optimal cut‐off value of C1R would allow sarcopenia diagnosis with 75% sensitivity and 66.67% specificity.ConclusionsOur results support the determination of EV PF4 and C1R as plasma diagnostic biomarkers in sarcopenia and open the door to investigate the role of the content of these vesicles in the pathogeny of the disease.
000136286 536__ $$9info:eu-repo/grantAgreement/ES/AEI/PID2022-140911OB-I00$$9info:eu-repo/grantAgreement/EC/H2020/752349 /EU/Nanoparticle-based immunization, a novel therapeutic strategy for amyotrophic lateral sclerosis/NanoALS$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 752349-NanoALS$$9info:eu-repo/grantAgreement/ES/ISCIII/CB12-03-30038$$9info:eu-repo/grantAgreement/ES/ISCIII/CB16-10-00477$$9info:eu-repo/grantAgreement/ES/ISCIII/CB18-05-0037$$9info:eu-repo/grantAgreement/ES/ISCIII/FEDER/PI21-00372$$9info:eu-repo/grantAgreement/ES/MINECO/DEP2016-78309-R$$9info:eu-repo/grantAgreement/ES/UZ/CUD2017-BIO-01$$9info:eu-repo/grantAgreement/ES/UZ/JIUZ-2021-BIO-05
000136286 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000136286 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000136286 700__ $$0(orcid)0000-0001-6523-5511$$aNavarrete-Villanueva, David$$uUniversidad de Zaragoza
000136286 700__ $$0(orcid)0000-0001-6492-2512$$aGómez-Cabello, Alba
000136286 700__ $$0(orcid)0000-0001-9802-8199$$aLópez-Royo, Tresa$$uUniversidad de Zaragoza
000136286 700__ $$aSantamaría, Enrique
000136286 700__ $$aFernández-Irigoyen, Joaquín
000136286 700__ $$aAusín, Karina
000136286 700__ $$0(orcid)0000-0003-3165-0156$$aArruebo, Manuel$$uUniversidad de Zaragoza
000136286 700__ $$0(orcid)0000-0002-6873-5244$$aSebastian, Victor$$uUniversidad de Zaragoza
000136286 700__ $$0(orcid)0000-0002-4303-4097$$aVicente-Rodríguez, Germán$$uUniversidad de Zaragoza
000136286 700__ $$0(orcid)0000-0001-5687-6704$$aOsta, Rosario$$uUniversidad de Zaragoza
000136286 700__ $$0(orcid)0000-0002-7477-8742$$aManzano, Raquel$$uUniversidad de Zaragoza
000136286 7102_ $$11001$$2420$$aUniversidad de Zaragoza$$bDpto. Anatom.,Embri.Genét.Ani.$$cÁrea Genética
000136286 7102_ $$11006$$2255$$aUniversidad de Zaragoza$$bDpto. Fisiatría y Enfermería$$cÁrea Enfermería
000136286 7102_ $$11006$$2245$$aUniversidad de Zaragoza$$bDpto. Fisiatría y Enfermería$$cÁrea Educación Física y Depor.
000136286 7102_ $$15005$$2555$$aUniversidad de Zaragoza$$bDpto. Ing.Quím.Tecnol.Med.Amb.$$cÁrea Ingeniería Química
000136286 773__ $$g(2024), [15 pp.]$$pJ. cachexia sarcopenia muscle$$tJournal of Cachexia, Sarcopenia and Muscle$$x2190-5991
000136286 8564_ $$s1554421$$uhttps://zaguan.unizar.es/record/136286/files/texto_completo.pdf$$yVersión publicada
000136286 8564_ $$s3012676$$uhttps://zaguan.unizar.es/record/136286/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000136286 909CO $$ooai:zaguan.unizar.es:136286$$particulos$$pdriver
000136286 951__ $$a2024-07-31-09:22:14
000136286 980__ $$aARTICLE