Correlations between clinical variables and gene-expression profiles in carotid plaque instability

Abstract

Objective: Strokes, a major cause of disability, are often caused by embolism from unstable carotid plaques. The aim of this study was to validate a biobank of human carotid endarterectomies as a platform for further exploration of pathways for plaque instability. For this purpose, we investigated the relationship between clinical parameters of plaque instability and expression of genes previously shown to be associated with either plaque instability or healing processes in the vessel wall.

Methods: A database of clinical information and gene-expression microarray data from 106 carotid endarterectomies were used.

Results: Expression of matrix metalloproteinase (MMP)-9 and MMP-7 was 100-fold higher in plaques than in normal artery. In general, genes associated with inflammation (such as RANKL and CD68) were overexpressed in symptomatic compared with asymptomatic plaques. Plaques obtained from patients undergoing surgery within 2 weeks after an embolic event showed up-regulation of genes involved in healing reactions in the vessel wall (including elastin and collagen). Statin treatment, as well as echodense lesions, were associated with a more stable phenotype.

Conclusion: Here, we demonstrate that gene-expression profiles reflect clinical parameters. Our results suggest that microarray technology and clinical variables can be used for the future identification of central molecular pathways in plaque instability.