title: Metabolites secreted by human atherothrombotic aneurysms revealed through a metabolomic approach.
abstract: Abdominal aortic aneurysm (AAA) is perma-nent and localized dilation of the abdominal aorta. Intraluminal thrombus (ILT) is involved in evolution and rupture of AAA. Complex biological processes associated with AAA include oxidative stress, proteolysis, neovascularization, aortic inflammation, cell death, and extracellular matrix breakdown. Biomarkers of growth and AAA rupture could give a more nuanced indication for surgery, unveil novel pathogenic pathways, and open possibilities for pharmacological inhibition of growth. Differential analysis of metabolites released by normal and pathological arteries in culture may help to find molecules that have a high probability of later being found in plasma and start signaling processes or be useful diagnostic/prognostic markers. We used a LC-QTOF-MS metabolomic approach to analyze metabolites released by human ILT (divided into luminal and abluminal layers), aneurysm wall (AW), and healthy wall (HW). Statistical analysis was used to compare luminal with abluminal ILT layer, ILT with AW, and AW with HW to select the metabolites exchanged between tissue and external medium. Identified compounds are related to inflammation and oxidative stress and indicate the possible role of fatty acid amides in AAA. Some metabolites (e.g., hippuric acid) had not been previously associated to aneurysm, others (fatty acid amides) have arisen, indicating a very promising line of research.
authors.affiliation: Centro de Excelencia en Metabolómica y Bioanálisis, Faculty of Pharmacy, University San Pablo-CEU, Campus Montepríncipe, Boadilla del Monte, 28668 Madrid, Spain.
authors.forename: Michal
authors.initials: M
authors.lastname: Ciborowski
authors.forename: Jose L
authors.initials: JL
authors.lastname: Martin-Ventura
authors.forename: Olivier
authors.initials: O
authors.lastname: Meilhac
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Michel
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Ruperez
authors.forename: Jose
authors.initials: J
authors.lastname: Tuñon
authors.forename: Jesus
authors.initials: J
authors.lastname: Egido
authors.forename: Coral
authors.initials: C
authors.lastname: Barbas
mesh_terms: D000577:Amides / Q000737:chemistry / Q000378:metabolism; D017544:Aortic Aneurysm, Abdominal / Q000378:metabolism* / Q000473:pathology; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D002853:Chromatography, Liquid / Q000379:methods; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D016018:Least-Squares Analysis; D055432:Metabolomics / Q000379:methods*; D015394:Molecular Structure; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods
chemical_list: D000577:Amides; D015415:Biomarkers; D005227:Fatty Acids