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

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

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Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden; School of Health and Social Studies, Dalarna University, Falun, Sweden.
Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden.
Department of Medical Sciences, Coagulation and Inflammation Science and Science for Life Laboratory Uppsala University, Uppsala, Sweden.
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:



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.


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.


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.


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.


Atherosclerosis; Carotid artery; Epidemiology; Proteomics; Ultrasound

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