Gene expression signatures, pathways and networks in XXXX .

@entity1 @entity32 @entity64 @entity12840 @entity10094 @entity4938 @entity15737 @entity2998 @entity730 @entity519 @entity1856 @entity731 @entity543 @entity6817 @entity20034
BACKGROUND: Embolism from unstable @entity1856 in the carotid bifurcation is a major cause of @entity64 . Here, we analysed gene expression in endarterectomies from @entity1 with symptomatic (S) and @entity10094 ( @entity10094 ) @entity543 to identify pathways linked to plaque instability. METHODS: Microarrays were prepared from plaques (n = 127) and peripheral blood samples (n = 96) of S and @entity10094 @entity1 . Gene set enrichment, pathway mapping and network analyses of differentially expressed genes were performed. RESULTS: These studies revealed upregulation of haemoglobin metabolism (P = 2.20E-05) and bone resorption (P = 9.63E-04) in S @entity1 . Analysis of subgroups of @entity1 indicated enrichment of @entity730 and osteoblast differentiation in S @entity1 on statins, as well as @entity32 and apoptosis in plaques removed >1 month compared to <2 weeks after symptom. By prediction profiling, a panel of 30 genes, mostly transcription factors, discriminated between plaques from S versus @entity10094 @entity1 with 78% accuracy. By meta-analysis, common gene networks associated with @entity731 mapped to @entity519 , chemokines, @entity730 , actin cytoskeleton and extracellular matrix. A set of dysregulated genes ( @entity12840 , @entity15737 , @entity20034 and @entity4938 ) previously not described in @entity731 were identified from microarrays and validated by quantitative PCR and immunohistochemistry. CONCLUSIONS: Our findings confirmed a central role for @entity32 and proteases in plaque instability, and highlighted haemoglobin metabolism and bone resorption as important pathways. Subgroup analysis suggested prolonged @entity32 following the symptoms of plaque instability and @entity730 as a possible stabilizing mechanism by @entity6817 . In addition, transcriptional regulation may play an important role in the determination of plaque phenotype. The results from this study will serve as a basis for further exploration of molecular signatures in @entity2998 .
