A Gene Expression Signature That Classifies Human Atherosclerotic Plaque by Relative Inflammation Status

Authors:
  • JYJeffrey Yuan
    Jeffrey Yuan
  • SSSergey Stepaniants
    Sergey Stepaniants
  • RZRenata Zieba
    Renata Zieba
  • EZEmanuel Zycband
    Emanuel Zycband
  • MMMark Morris
    Mark Morris
  • SCSilvija Coulter
    Silvija Coulter
  • XYXiang Yu
    Xiang Yu
  • JMJohn Menke
    John Menke
  • JWJohn Woods
    John Woods
  • FCFabian Chen
    Fabian Chen
  • DRDena R. Ramey
    Dena R. Ramey
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Abstract
Background—: Atherosclerosis is a complex disease requiring improvements in diagnostic techniques and therapeutic treatments. Both improvements will be facilitated by greater exploration of the biology of atherosclerotic plaque. To this end, we carried out large-scale gene expression analysis of human atherosclerotic lesions. Methods and Results—: Whole genome expression analysis of 101 plaques from patients with peripheral artery disease identified a robust gene signature (1514 genes) that is dominated by processes related to Toll-like receptor signaling, T-cell activation, cholesterol efflux, oxidative stress response, inflammatory cytokine production, vasoconstriction, and lysosomal activity. Further analysis of gene expression in microdissected carotid plaque samples revealed that this signature is differentially expressed in macrophage-rich and smooth muscle cell–containing regions. A quantitative PCR gene expression panel and inflammatory composite score were developed on the basis of the atherosclerotic plaque gene signature. When applied to serial sections of carotid plaque, the inflammatory composite score was observed to correlate with histological and morphological features related to plaque vulnerability. Conclusions—: The robust mRNA expression signature identified in the present report is associated with pathological features of vulnerable atherosclerotic plaque and may be useful as a source of biomarkers and targets of novel antiatherosclerotic therapies.

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