Dissecting the mechanism of carotid atherosclerosis from the perspective of regulation

Int J Mol Med. 2014 Dec;34(6):1458-66. doi: 10.3892/ijmm.2014.1960. Epub 2014 Oct 9.

Abstract

Carotid atherosclerosis is a chronic inflammatory disease of the arterial wall. The present study aimed to identify changes in the gene expression and regulatory factors for atherosclerotic plaques of carotid atherosclerosis from an early to an advanced stage. The original data were downloaded from the NCBI GEO database under accession no. GSE28829. Differentially expressed genes (DEGs) were detected by the Robust Multiarray Average (RMA). The enriched Gene Ontology (GO) terms and pathways for DEGs using DAVID were subsequently identified. The transcriptional and microRNA (miRNA) regulatory network were constructed for the DEGs. Cis-regulatory signals were also investigated. More genes were activated in the advanced stage compared with the early stage. IGHG1 and SPP1 were upregulated, while MYBL1 and PLD were downregulated. The upregulated genes in the advanced stage were involved in atherosclerosis‑related GO terms such as immune, vascular and cell movement homeostasis. The DEGs were significantly enriched in cell adhesion molecules (CAMs) and the focal adhesion pathway. MMP9 and CFL2 played key roles in the transcriptional regulatory network. Moreover, miR-328 was identified as one of the hubs in the miRNA regulatory network. The results may therefore be used to determine the mechanism involved in carotid atherosclerosis.

MeSH terms

  • Carotid Artery Diseases / genetics*
  • Carotid Artery Diseases / pathology
  • Cofilin 2 / genetics
  • Databases, Genetic
  • Gene Ontology
  • Gene Regulatory Networks*
  • Humans
  • Matrix Metalloproteinase 9 / genetics
  • MicroRNAs / genetics
  • Models, Genetic
  • Oligonucleotide Array Sequence Analysis
  • Signal Transduction / genetics*
  • Transcriptome / genetics*

Substances

  • CFL2 protein, human
  • Cofilin 2
  • MIRN328 microRNA, human
  • MicroRNAs
  • Matrix Metalloproteinase 9