Blood genomic profiling in extracranial- and intracranial atherosclerosis in ischemic stroke patients

Abstract

Objective: Extracranial- and intracranial atherosclerosis (ECAS and ICAS) have been suggested to have different pathogeneses. Blood genomic profiling may identify their unique molecular signatures.

Methods: Whole gene microarray of peripheral blood was performed in 24 patients with acute ischemic stroke (ECAS, n=12; ICAS, n=12) and 12 healthy controls. Differential gene expression and gene set enrichment analysis (GSEA) were conducted. Plasma resistin levels were compared across independent samples of stroke patients with ECAS (n=39), ICAS (n=20), and small vessel disease (SVD, n=57).

Results: Microarray revealed that 144 and 24 transcripts were altered in ECAS and ICAS, respectively, compared to controls. All the transcripts that were differentially expressed in ICAS were also differentially expressed in ECAS. A total of 120 transcripts were differentially expressed only in ECAS. Gene sets related to immune response and protein metabolism were altered in both ECAS and ICAS, but the magnitude of gene alteration was higher in ECAS than in ICAS. Several genes of interest including RETN, IRF5, CD163, and CHST13 were more highly expressed in ECAS than in ICAS. Circulating resistin levels were elevated in independent samples of ECAS, but not in those of ICAS, compared to those of SVDs.

Conclusions: ECAS showed prominent genomic alteration related to immune response compared to ICAS. Although there was no ECAS-specific gene to be identified on microarray, the level of resistin expression was high on peripheral blood in ECAS, suggesting that resistin is associated with the pathogenesis of ECAS.

Keywords: Extracranial atherosclerosis; Gene expression; Intracranial atherosclerosis; Microarray; Stroke.