Carotid artery disease: novel pathophysiological mechanisms identified by gene-expression profiling of peripheral blood

OBJECT: The pathogenesis of carotid artery stenosis (CAS) as well as the mechanisms underlying the different localisation of the atherosclerotic lesions remains poorly understood. We used microarray technology to identify novel systemic mediators that could contribute to CAS pathogenesis. Moreover, we compared gene-expression profile of CAS with that of patients affected by abdominal aortic aneurysm (AAA), previously published by our group. METHODS AND RESULTS: By global gene-expression profiling in a pool of 10 CAS patients and 10 matched controls, we found 82 genes differentially expressed. Validation study in pools used for profiling and replication study in larger numbers of CAS patients (n = 40) and controls (n = 40) of 14 genes by real-time polymerase chain reaction (RT-PCR) confirmed microarray results. Fourteen out of 82 genes were similarly expressed in AAA patients. Gene ontology analysis identified a statistically significant enrichment in CAS of differentially expressed transcripts involved in immune response and oxygen transport. Whereas alteration of oxygen transport is a common tract of the two localisations, alteration of immune response in CAS and of lipid metabolic process in AAA represents distinctive tracts of the two atherosclerotic diseases. CONCLUSIONS: We describe the systemic gene-expression profile of CAS, which provides an extensive list of potential molecular markers.