Department of Clinical Chemistry, Tampere University Hospital, Fimlab Laboratories and University of Tampere, School of Medicine, Finland.
Heart Center, Department of Cardio-Thoracic Surgery, Tampere University Hospital and University of Tampere, School of Medicine, Tampere, Finland.
Sci Rep. 2017 Jan 27;7:41483. doi: 10.1038/srep41483.
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.
由于动脉粥样硬化导致的心血管疾病是全球范围内的主要死亡原因。我们旨在研究与健康对照动脉相比,晚期外周动脉粥样硬化斑块中潜在改变的基因和通路表达。对来自坦佩雷血管研究的 68 个晚期动脉粥样硬化斑块(15 个主动脉、29 个颈动脉和 24 个股动脉斑块)和 28 个对照(左内乳动脉(LITA))进行了基因表达分析(Illumina HumanHT-12 版本 3 表达珠芯片)。个体基因的失调与健康对照进行了比较,并在不同动脉床的斑块之间进行了比较,并对 fold change (FC) > ±1.5 和 false discovery rate (FDR) < 0.05 的基因进行了 Ingenuity 通路分析。787 个基因在动脉粥样硬化斑块中差异表达。上调最明显的基因是骨桥蛋白和多个 MMPs,下调最明显的是细胞死亡诱导 DFFA 样效应因子 C 和 A (CIDEC, CIDEA) 和载脂蛋白 D (FC > 20)。156 条通路在动脉粥样硬化斑块中差异表达,主要与炎症有关,特别是与白细胞迁移和信号转导有关。在动脉特异性斑块分析中,三个动脉床共有 50.4%的经典通路和 41.2%的 GO 术语差异表达。我们的结果证实了晚期动脉粥样硬化的炎症性质,并显示了不同动脉床之间的新的通路差异。