Histologically Unstable Asymptomatic Carotid Plaques Have Altered Expression of Genes Involved in Chemokine Signalling Leading to Localised Plaque Inflammation and Rupture

WHAT THIS PAPER ADDS? This is the first study to use a whole genomic approach to analyse the gene expression profile of histologically unstable carotid atherosclerotic plaques compared to stable plaques in neurologically asymptomatic patients. We have demonstrated in asymptomatic patients as previously shown in symptomatic patients that patients with histologically unstable plaques have altered expression of genes related to inflammation and immune response. The altered gene expression profile found may lead to changes in chemokine signalling and plaque rupture. Novel gene clusters related to intra-cellular signalling and alterations in transcription identified from this study are potential areas for further research. 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 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