title: Differentially expressed genes and canonical pathway expression in human atherosclerotic plaques - Tampere Vascular Study.
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.
authors.affiliation: Department of Clinical Chemistry, Tampere University Hospital, Fimlab Laboratories and University of Tampere, School of Medicine, Finland.
authors.forename: Miska
authors.initials: M
authors.lastname: Sulkava
authors.affiliation: Department of Clinical Chemistry, Tampere University Hospital, Fimlab Laboratories and University of Tampere, School of Medicine, Finland.
authors.forename: Emma
authors.initials: E
authors.lastname: Raitoharju
authors.affiliation: Department of Clinical Chemistry, Tampere University Hospital, Fimlab Laboratories and University of Tampere, School of Medicine, Finland.
authors.forename: Mari
authors.initials: M
authors.lastname: Levula
authors.affiliation: Department of Clinical Chemistry, Tampere University Hospital, Fimlab Laboratories and University of Tampere, School of Medicine, Finland.
authors.forename: Ilkka
authors.initials: I
authors.lastname: Seppälä
authors.affiliation: Department of Clinical Chemistry, Tampere University Hospital, Fimlab Laboratories and University of Tampere, School of Medicine, Finland.
authors.forename: Leo-Pekka
authors.initials: LP
authors.lastname: Lyytikäinen
authors.affiliation: Heart Center, Department of Cardio-Thoracic Surgery, Tampere University Hospital and University of Tampere, School of Medicine, Tampere, Finland.
authors.forename: Ari
authors.initials: A
authors.lastname: Mennander
authors.affiliation: Heart Center, Department of Cardio-Thoracic Surgery, Tampere University Hospital and University of Tampere, School of Medicine, Tampere, Finland.
authors.forename: Otso
authors.initials: O
authors.lastname: Järvinen
authors.affiliation: Division of Vascular Surgery, Department of Surgery, Tampere University Hospital, Finland.
authors.forename: Rainer
authors.initials: R
authors.lastname: Zeitlin
authors.affiliation: Division of Vascular Surgery, Department of Surgery, Tampere University Hospital, Finland.
authors.forename: Juha-Pekka
authors.initials: JP
authors.lastname: Salenius
authors.affiliation: Research Unit of Molecular Epidemiology, Helmholtz Zentrum, German Research Center for Environmental Health, Munich, Germany.|Hannover Unified Biobank, Hannover Medical School, Hannover, Germany.|Institute for Human Genetics, Hannover Medical School, Hanover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.affiliation: Research Unit of Molecular Epidemiology, Helmholtz Zentrum, German Research Center for Environmental Health, Munich, Germany.|Hannover Unified Biobank, Hannover Medical School, Hannover, Germany.
authors.forename: Norman
authors.initials: N
authors.lastname: Klopp
authors.affiliation: Department of Clinical Chemistry, Tampere University Hospital, Fimlab Laboratories and University of Tampere, School of Medicine, Finland.
authors.forename: Nina
authors.initials: N
authors.lastname: Mononen
authors.affiliation: Department of Clinical Chemistry, Tampere University Hospital, Fimlab Laboratories and University of Tampere, School of Medicine, Finland.
authors.forename: Reijo
authors.initials: R
authors.lastname: Laaksonen
authors.affiliation: Department of Clinical Physiology, Tampere University Hospital and University of Tampere, School of Medicine, Finlan.
authors.forename: Mika
authors.initials: M
authors.lastname: Kähönen
authors.affiliation: Department of Clinical Chemistry, Tampere University Hospital, Fimlab Laboratories and University of Tampere, School of Medicine, Finland.|Division of Vascular Surgery, Department of Surgery, Tampere University Hospital, Finland.
authors.forename: Niku
authors.initials: N
authors.lastname: Oksala
authors.affiliation: Department of Clinical Chemistry, Tampere University Hospital, Fimlab Laboratories and University of Tampere, School of Medicine, Finland.
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
mesh_terms: D050197:Atherosclerosis / Q000235:genetics; D016022:Case-Control Studies; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D058226:Plaque, Atherosclerotic / Q000235:genetics*; D013895:Thoracic Arteries / Q000473:pathology