Metabolomics with LC-QTOF-MS Permits the Prediction of Disease Stage in Aortic Abdominal Aneurysm Based on Plasma Metabolic Fingerprint 英文参考文献.docVIP

MetabolomicswithLC-QTOF-MSPermitsthePrediction ofDiseaseStageinAorticAbdominalAneurysmBased onPlasmaMetabolicFingerprint MichalCiborowski1,2,JoannaTeul1,3,JoseLuisMartin-Ventura4,5,Jesu′sEgido4,5,CoralBarbas1* 1CEMBIO (Center for Metabolomics and Bioanalysis), Facultad de Farmacia, Universidad CEU San Pablo, Madrid, Spain, 2Department of Physical Chemistry, Medical UniversityofBialystok,Bialystok,Poland,3DepartmentofPharmaceuticalAnalysis,MedicalUniversityofBialystok,Bialystok,Poland,4VascularResearchLaboratory,IIS- Fundacio′nJime′nez D?′az,Madrid,Spain,5Auto′nomaUniversity,Madrid,Spain Abstract Abdominalaorticaneurysm(AAA)isapermanentandlocalizedaorticdilation,definedasaorticdiameter$3cm.Itisan asymptomatic but potentially fatal condition because progressive enlargement of the abdominal aorta is spontaneously evolvingtowardsrupture.BiomarkersmayhelptoexplainpathologicalprocessesofAAAexpansion,andallowustofind noveltherapeuticstrategiesortodeterminetheefficiencyofcurrenttherapies.Metabolomicsseemstobeagoodapproach to find biomarkers of AAA. In this study, plasma samples of patients with large AAA, small AAA, and controls were fingerprintedwithLC-QTOF-MS.Statisticalanalysiswasusedtocomparemetabolicfingerprintsandselectmetabolitesthat showed a significant change. Results presented here reveal that LC-QTOF-MS based fingerprinting of plasma from AAA patients is a very good technique to distinguish small AAA, large AAA, and controls. With the use of validated PLS-DA modelsitwaspossibletoclassifypatientsaccordingtothediseasestageandpredictproperlythestageofadditionalAAA patients. Identified metabolites indicate a role for sphingolipids, lysophospholipids, cholesterol metabolites, and acylcarnitines in the development and progression of AAA. Moreover, guanidinosuccinic acid, which mimics nitric oxide intermsofitsvasodilatoryaction,wasfoundasastrongmarkeroflargeAAA. Citation:CiborowskiM,TeulJ,Martin-VenturaJL,EgidoJ,BarbasC(2012)MetabolomicswithLC-QTOF-MSPermitsthePredic