title: Use of a proximity extension assay proteomics chip to discover new biomarkers for human atherosclerosis.
abstract: OBJECTIVE
  We used a proteomics array to simultaneously measure multiple proteins that have been suggested to be associated with atherosclerosis and related them to plaque prevalence in carotid arteries in a human population-based study.
  
  
  METHODS
  In the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS; n = 931, 50% women, all aged 70 years), the number of carotid arteries with plaques was recorded by ultrasound. Levels of 82 proteins were assessed in plasma by a proximity extension assay (Proseek Multiplex CVD, Olink Bioscience, Uppsala, Sweden) and related to carotid measures in a regression framework.
  
  
  RESULTS
  Following adjustment for multiple testing with Bonferroni correction, seven of the proteins were significantly related to the number of carotid arteries affected by plaques in sex-adjusted models (osteoprotegrin, T-cell immunoglobulin and mucin domain (TIM)-1, growth/differentiation factor 15 (GDF-15), matrix metalloprotease-12 (MMP-12), renin, tumor necrosis factor ligand superfamily member 14 (TNFSF14) and growth hormone). Of these, renin (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.13-1.49 per standard deviation increase), growth hormone (OR, 1.24; 95% CI, 1.08-1.43), osteoprotegerin (OR, 1.22; 95% CI, 1.05-1.43) and TNFSF14 (OR, 1.17; 95% CI, 1.01-1.35) were related to plaque prevalence independently of each other and traditional cardiovascular risk factors.
  
  
  CONCLUSIONS
  A novel targeted proteomics approach using the proximity extension technique discovered several new associations of candidate proteins with carotid artery plaque prevalence in a large human sample.
authors.affiliation: Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Lind
authors.affiliation: Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden; School of Health and Social Studies, Dalarna University, Falun, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Ärnlöv
authors.affiliation: Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden.
authors.forename: Bertil
authors.initials: B
authors.lastname: Lindahl
authors.affiliation: Department of Medical Sciences, Coagulation and Inflammation Science and Science for Life Laboratory Uppsala University, Uppsala, Sweden.
authors.forename: Agneta
authors.initials: A
authors.lastname: Siegbahn
authors.affiliation: Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Sundström
authors.affiliation: Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden; Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: erik.ingelsson@medsci.uu.se.
authors.forename: Erik
authors.initials: E
authors.lastname: Ingelsson
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000032:analysis*; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000378:metabolism*; D002340:Carotid Artery Diseases / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D059168:Carotid Intima-Media Thickness; D005260:Female; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D058226:Plaque, Atherosclerotic; D011237:Predictive Value of Tests; D015995:Prevalence; D011446:Prospective Studies; D040081:Protein Array Analysis; D040901:Proteomics / Q000379:methods*; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D001798:Blood Proteins
keywords: Atherosclerosis; Carotid artery; Epidemiology; Proteomics; Ultrasound