title: New Biochemical Insights into the Mechanisms of Pulmonary Arterial Hypertension in Humans.
abstract: Diagnosis 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.
authors.affiliation: Centre of Metabolomics and Bioanalysis (CEMBIO), Facultad de Farmacia, Universidad CEU San Pablo, Campus Monteprincipe, Boadilla del Monte, Madrid, Spain.|Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416, Gdańsk, Poland.
authors.forename: Renata
authors.initials: R
authors.lastname: Bujak
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.|Ciber de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Mateo
authors.affiliation: Hospital Clinic Barcelona-IDIBAPS, Barcelona, Spain.|Ciber de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Blanco
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.|Ciber de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Izquierdo-García
authors.affiliation: Centre of Metabolomics and Bioanalysis (CEMBIO), Facultad de Farmacia, Universidad CEU San Pablo, Campus Monteprincipe, Boadilla del Monte, Madrid, Spain.
authors.forename: Danuta
authors.initials: D
authors.lastname: Dudzik
authors.affiliation: Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416, Gdańsk, Poland.
authors.forename: Michał J
authors.initials: MJ
authors.lastname: Markuszewski
authors.affiliation: Hospital Clinic Barcelona-IDIBAPS, Barcelona, Spain.|Ciber de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Victor Ivo
authors.initials: VI
authors.lastname: Peinado
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.|CIBERESP, Preventive Medicine and Public Health Department, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Martín
authors.initials: M
authors.lastname: Laclaustra
authors.affiliation: Hospital Clinic Barcelona-IDIBAPS, Barcelona, Spain.|Ciber de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Joan Albert
authors.initials: JA
authors.lastname: Barberá
authors.affiliation: Centre of Metabolomics and Bioanalysis (CEMBIO), Facultad de Farmacia, Universidad CEU San Pablo, Campus Monteprincipe, Boadilla del Monte, Madrid, Spain.
authors.forename: Coral
authors.initials: C
authors.lastname: Barbas
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.|Ciber de Enfermedades Respiratorias (CIBERES), Madrid, Spain.|Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Jesús
authors.identifier: http://orcid.org/0000-0001-8681-5056
authors.initials: J
authors.lastname: Ruiz-Cabello
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000378:metabolism*; D001774:Blood Chemical Analysis / Q000379:methods; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis* / Q000378:metabolism*; D008297:Male; D055432:Metabolomics / Q000379:methods*; D013030:Spain
chemical_list: D015415:Biomarkers