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Gene expression differences between stroke-associated and asymptomatic carotid plaques

世界最新医学信息文摘 2015年第5期 7-7页

作者： Jani Saksi Petra Ij s Krista Nuotio Riitta Sonninen Lauri Soinne Oili Salonen Eija Saimanen jarno tuimala Erno M.Lehtonen-Smeds Markku Kaste Petri T.Kovanen Perttu J.Lindsberg

Atherosclerotic carotid stenosis is an important risk factor for stroke. Carotid plaques(CPs) causing stroke may present a distinct type of molecular pathology compared with transient ischemic attack( TIA)-associated or asymptomatic plaques. We compared the gene expression profiles of CPs from stroke patients( n =12) and asymptomatic patients( n =9),both with similar risk factors and severity of carotid stenosis(>70%). Sixty probes showed over 1.5-fold expression difference at 5% false discovery rate. Functional clustering showed enrichment of genes in 51 GO categories and seven pathways, the most significant of which relate to extracellular-matrix interaction, PPAR gamma signaling, scavanger receptor activity, and lysosomal activity. Differential expression of ten genes was confirmed in an extended replication group(n=43), where the most significant expression differences were found in CD36( 2.1-fold change, p =0.005), CD163( 1.7-fold change, p =0.007) and FABP4(2.2-fold change, p=0.015). These include four genes not previously linked to plaque destabilization: GLUL(2.2-fold change,p=0.016), FUCA1(2.2-fold change, p=0.025), IL1RN(1.6-fold change, p=0.034), and S100A8(2.5-fold change, p=0.047). Strong correlations were found to plaque ulceration, plaque hemorrhage, and markers of apoptosis and proliferation(activated caspase 3, TUNEL, and Ki67). Protein expression of these genes was confirmed by immunohistochemistry and was found in the atheromatous areas of CPs critical for plaque destabilization. This study presents a comprehensive transcriptional analysis of stroke-associated CPs and demonstrates a significant transcriptome difference between stroke-associated and asymptomatic CPs. Followup studies on the identified genes are needed to define whether they could be used as biomarkers of symptomatic CPs or have a role in plaque destabilization.

关键词： Stroke Atherosclerosis Microarray Cerebrovascular Real-time PCR

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