Use of a proximity extension assay proteomics chip to discover new biomarkers for human atherosclerosis

Atherosclerosis. 2015 Sep;242(1):205-10. doi: 10.1016/j.atherosclerosis.2015.07.023. Epub 2015 Jul 14.


Background and aims: 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.

Conclusion: 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.

Keywords: Atherosclerosis; Carotid artery; Epidemiology; Proteomics; Ultrasound.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • Blood Proteins / analysis*
  • Carotid Arteries / diagnostic imaging
  • Carotid Arteries / metabolism*
  • Carotid Artery Diseases / blood*
  • Carotid Artery Diseases / diagnosis
  • Carotid Artery Diseases / epidemiology
  • Carotid Intima-Media Thickness
  • Female
  • Humans
  • Linear Models
  • Logistic Models
  • Male
  • Odds Ratio
  • Plaque, Atherosclerotic
  • Predictive Value of Tests
  • Prevalence
  • Prospective Studies
  • Protein Array Analysis*
  • Proteomics / methods*
  • Risk Factors
  • Sweden / epidemiology


  • Biomarkers
  • Blood Proteins