title: Quantitative HDL Proteomics Identifies Peroxiredoxin-6 as a Biomarker of Human Abdominal Aortic Aneurysm.
abstract: High-density lipoproteins (HDLs) are complex protein and lipid assemblies whose composition is known to change in diverse pathological situations. Analysis of the HDL proteome can thus provide insight into the main mechanisms underlying abdominal aortic aneurysm (AAA) and potentially detect novel systemic biomarkers. We performed a multiplexed quantitative proteomics analysis of HDLs isolated from plasma of AAA patients (N = 14) and control study participants (N = 7). Validation was performed by western-blot (HDL), immunohistochemistry (tissue), and ELISA (plasma). HDL from AAA patients showed elevated expression of peroxiredoxin-6 (PRDX6), HLA class I histocompatibility antigen (HLA-I), retinol-binding protein 4, and paraoxonase/arylesterase 1 (PON1), whereas α-2 macroglobulin and C4b-binding protein were decreased. The main pathways associated with HDL alterations in AAA were oxidative stress and immune-inflammatory responses. In AAA tissue, PRDX6 colocalized with neutrophils, vascular smooth muscle cells, and lipid oxidation. Moreover, plasma PRDX6 was higher in AAA (N = 47) than in controls (N = 27), reflecting increased systemic oxidative stress. Finally, a positive correlation was recorded between PRDX6 and AAA diameter. The analysis of the HDL proteome demonstrates that redox imbalance is a major mechanism in AAA, identifying the antioxidant PRDX6 as a novel systemic biomarker of AAA.
authors.affiliation: Vascular Research Lab, IIS-Fundación Jiménez Díaz-Autonoma University, Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Burillo
authors.affiliation: Cardiovascular Proteomics Laboratory, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Jorge
authors.affiliation: Vascular Research Lab, IIS-Fundación Jiménez Díaz-Autonoma University, Madrid, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Martínez-López
authors.affiliation: Cardiovascular Proteomics Laboratory, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Camafeita
authors.affiliation: Vascular Research Lab, IIS-Fundación Jiménez Díaz-Autonoma University, Madrid, Spain.
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Blanco-Colio
authors.affiliation: Cardiovascular Proteomics Laboratory, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
authors.forename: Marco
authors.initials: M
authors.lastname: Trevisan-Herraz
authors.affiliation: Cardiovascular Proteomics Laboratory, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
authors.forename: Iakes
authors.initials: I
authors.lastname: Ezkurdia
authors.affiliation: Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Egido
authors.affiliation: Inserm, U698, Universite Paris 7, CHU X-Bichat, Paris, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Michel
authors.affiliation: Diabète athérothrombose Thérapies Réunion Océan Indien (UMR DéTROI U1188) - Université de La Réunion-CYROI- 2, rue Maxime Rivière 97490 Sainte Clotilde - La Réunion - France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Meilhac
authors.affiliation: Cardiovascular Proteomics Laboratory, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Vázquez
authors.affiliation: Vascular Research Lab, IIS-Fundación Jiménez Díaz-Autonoma University, Madrid, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Martin-Ventura
mesh_terms: D000368:Aged; D017544:Aortic Aneurysm, Abdominal / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*; D015415:Biomarkers; D002853:Chromatography, Liquid; D015897:Comorbidity; D019295:Computational Biology / Q000379:methods; D005260:Female; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D054465:Peroxiredoxin VI / Q000097:blood / Q000378:metabolism*; D020543:Proteome; D040901:Proteomics / Q000379:methods; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry; D057188:Workflow
chemical_list: D015415:Biomarkers; D008075:Lipoproteins, HDL; D020543:Proteome; D054465:Peroxiredoxin VI