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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.

Author information

1
Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
2
Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden; School of Health and Social Studies, Dalarna University, Falun, Sweden.
3
Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden.
4
Department of Medical Sciences, Coagulation and Inflammation Science and Science for Life Laboratory Uppsala University, Uppsala, Sweden.
5
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.

Abstract

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

[Indexed for MEDLINE]

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