Histologically unstable asymptomatic carotid plaques have altered expression of genes involved in chemokine signalling leading to localised plaque inflammation and rupture

Eur J Vasc Endovasc Surg. 2013 Feb;45(2):121-7. doi: 10.1016/j.ejvs.2012.11.006. Epub 2012 Dec 21.


Background: Many studies have evaluated histological and gene expression profiles in TIA/stroke patients after onset of symptoms, but there is limited understanding as to how these plaque related features interact before symptom onset. In particular, no studies have evaluated differential gene expression in histologically unstable (vs stable plaques) in neurologically asymptomatic patients.

Methods: Nine asymptomatic patients had their plaques scored blindly by two independent Histopathologists using the AHA plaque scoring system. RNA extracted from the plaques was hybridised onto a whole genome microarray. Analysis was performed using GenomeStudio (v1.0) and the DAVID bioinformatics resource (v6.7).

Results: Three plaques were histologically unstable (Grade 2/3), while six were stable (Grade 0/1). 346 differentially expressed genes (>1.3 fold, P < 0.05) were identified (293 down-regulated and 53 up-regulated) between stable and unstable plaques. Genes related to chemokine and protein signalling (pro-inflammatory/pro-apoptotic) were identified to have high enrichment scores (>1.3) and were significantly up-regulated in unstable (asymptomatic) plaques.

Conclusion: The findings confirm the intuitively held belief that changes in chemokine and protein signalling may be associated with acute plaque disruption and precede the onset of symptoms. Once validated, these genes could therefore become targets for innovative medical treatments in the future or could help identify asymptomatic patients with histologically unstable plaques that would benefit from surgical intervention.

MeSH terms

  • Aged
  • Apoptosis / genetics
  • Asymptomatic Diseases
  • Carotid Arteries / immunology*
  • Carotid Arteries / pathology
  • Carotid Arteries / surgery
  • Carotid Stenosis / complications
  • Carotid Stenosis / genetics*
  • Carotid Stenosis / immunology
  • Carotid Stenosis / pathology
  • Carotid Stenosis / surgery
  • Chemokines / genetics*
  • Chi-Square Distribution
  • Cluster Analysis
  • Disease Progression
  • Endarterectomy, Carotid
  • Female
  • Gene Expression Profiling / methods
  • Gene Expression Regulation
  • Humans
  • Inflammation / genetics*
  • Inflammation / immunology
  • Inflammation / pathology
  • Inflammation Mediators / analysis*
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Plaque, Atherosclerotic
  • Rupture, Spontaneous
  • Severity of Illness Index
  • Signal Transduction / genetics*


  • Chemokines
  • Inflammation Mediators