Differentially expressed genes and canonical pathway expression in human atherosclerotic plaques - Tampere Vascular Study

Sulkava, M; Raitoharju, E; Levula, M; Seppala, I; Lyytikainen, LP; Mennander, A; Jarvinen, O; Zeitlin, R; Salenius, JP; Illig, T; Klopp, N; Mononen, N; Laaksonen, R; Kahonen, M; Oksala, N; Lehtimaki, T

Sulkava, M (reprint author), Tampere Univ Hosp, Dept Clin Chem, Fimlab Labs, Tampere, Finland.; Sulkava, M (reprint author), Univ Tampere, Sch Med, Tampere, Finland.

Scientific Reports, 2017; 7 ( ):

Abstract

Cardiovascular diseases due to atherosclerosis are the leading cause of death globally. We aimed to investigate the potentially altered gene and pathway expression in advanced peripheral atherosclerotic plaques in comparison to healthy control arteries. Gene expression analysis was performed (Illumina HumanHT-12 version 3 Expression BeadChip) for 68 advanced atherosclerotic plaques (15 aortic, 29 carotid and 24 femoral plaques) and 28 controls (left internal thoracic artery (LITA)) from Tampere Vascular Study. Dysregulation of individual genes was compared to healthy controls and between plaques from different arterial beds and Ingenuity pathway analysis was conducted on genes with a fold change (FC) > +/- 1.5 and false discovery rate (FDR) < 0.05. 787 genes were significantly differentially expressed in atherosclerotic plaques. The most up-regulated genes were osteopontin and multiple MMPs, and the most down-regulated were cell death-inducing DFFA-like effector C and A (CIDEC, CIDEA) and apolipoprotein D (FC > 20). 156 pathways were differentially expressed in atherosclerotic plaques, mostly inflammation-related, especially related with leukocyte trafficking and signaling. In artery specific plaque analysis 50.4% of canonical pathways and 41.2% GO terms differentially expressed were in common for all three arterial beds. Our results confirm the inflammatory nature of advanced atherosclerosis and show novel pathway differences between different arterial beds.

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