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dc.contributor.authorBujak, Renata
dc.contributor.authorMateo, Jesus 
dc.contributor.authorBlanco, Isabel
dc.contributor.authorIzquierdo-Garcia, Jose L. 
dc.contributor.authorDudzik, Danuta
dc.contributor.authorMarkuszewski, Michal J.
dc.contributor.authorIvo Peinado, Victor
dc.contributor.authorLaclaustra, Martin 
dc.contributor.authorAlbert Barbera, Joan
dc.contributor.authorBarbas, Coral
dc.contributor.authorRuiz-Cabello, Jesus 
dc.date.accessioned2017-10-30T13:15:40Z
dc.date.available2017-10-30T13:15:40Z
dc.date.issued2016
dc.identifierISI:000381367800080
dc.identifier.citationPLoS One. 2016; 11(8):e0160505
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/20.500.12105/5205
dc.description.abstractDiagnosis of pulmonary arterial hypertension (PAH) is difficult due to the lack of specific clinical symptoms and biomarkers, especially at early stages. We compared plasma metabolic fingerprints of PAH patients (n = 20) with matched healthy volunteers (n = 20) using, for the first time, untargeted multiplatform metabolomics approach consisting of high-performance liquid and gas chromatography coupled with mass spectrometry. Multivariate statistical analyses were performed to select metabolites that contribute most to groups' classification (21 from liquid in both ionization modes and 9 from gas chromatography-mass spectrometry). We found metabolites related to energy imbalance, such as glycolysis-derived metabolites, as well as metabolites involved in fatty acid, lipid and amino acid metabolism. We observed statistically significant changes in threitol and aminomalonic acid in PAH patients, which could provide new biochemical insights into the pathogenesis of the disease. The results were externally validated on independent case and control cohorts, confirming up to 16 metabolites as statistically significant in the validation study. Multiplatform metabolomics, followed by multivariate chemometric data analysis has a huge potential for explaining pathogenesis of PAH and for searching potential and new more specific and less invasive markers of the disease.
dc.description.sponsorshipThis research was supported by the Polish National Science Center (2014/13/N/NZ7/04231), the Spanish Ministry of Economy and Competitiveness (MINECO) (SAF2014-58920R), by the Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III and co-funding by Fondo Europeo de Desarrollo Regional (FEDER) (PI14-01427), and by the quality-promoting subsidy from the Ministry of Science and Higher Education of Poland, Leading National Research Centre (KNOW programme 2012-2017). The CNIC is supported by the Spanish Ministry of Economy and Competitiveness and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
dc.language.isoeng
dc.publisherPUBLIC LIBRARY SCIENCE
dc.relation.isversionofPublisher's version
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectALPHA PPAR-ALPHA
dc.subjectENDOTHELIAL-CELLS
dc.subjectPATHWAY
dc.subjectGLUTAMINOLYSIS
dc.subjectMETABOLISM
dc.subjectRELEVANCE
dc.subjectOXIDATION
dc.subjectPLASMA
dc.subjectACID
dc.titleNew Biochemical Insights into the Mechanisms of Pulmonary Arterial Hypertension in Humans
dc.typeArtículo
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID27486806
dc.format.volume11
dc.identifier.doi10.1371/journal.pone.0160505
dc.contributor.funderNational Science Centre (Poland)
dc.contributor.funderMinisterio de Economía y Competitividad (España)
dc.contributor.funderInstituto de Salud Carlos III - ISCIII
dc.contributor.funderEuropean Regional Development Fund (ERDF/FEDER)
dc.contributor.funderMinistry of Science and Higher Education (Poland)
dc.contributor.funderFundación ProCNIC
dc.description.peerreviewed
dc.relation.publisherversionhttps://doi.org/10.1371/journal.pone.0160505
dc.identifier.journalPlos One
dc.repisalud.orgCNICCNIC::Unidades técnicas::Imagen Avanzada
dc.repisalud.institucionCNIC
dc.relation.projectIDMINECO/ICTI2013-2016/SAF2014-58920Res_ES
dc.relation.projectIDMINECO/ICTI2013-2016/SEV-2015-0505es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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