Transcriptome-wide characterization of gene expression associated with unruptured intracranial aneurysms

The biological mechanisms by which cerebral aneurysms emerge, enlarge and rupture are not totally understood. In the present study, we analyzed the genome-wide gene expression profile in human intracranial aneurysms using cDNA microarrays.

Affymetrix HU133 Plus 2.0 microarrays were used to compare gene expression levels between human cerebral aneurismal samples and normal blood vessels. Raw data were evaluated by GeneSpring software version 9.05. Differentially expressed genes were further classified according to the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes annotations. Quantitative real-time polymerase chain reaction was used to confirm the microarray results.

Clustering analysis demonstrated that the aneurysm tissues and control tissues were clearly separated into two distinct groups according the differential expression patterns. The levels of 1,160 genes were significantly changed. Of these genes, 164 were upregulated and 996 were downregulated. A cluster of extracellular matrix related genes, including collagens (type I, III, V, and XI) and metalloproteinases were significantly upregulated. In contrast to previous reports, we found that a number of immune/inflammation-related genes were downregulated in intracranial aneurysms.

Human cerebral aneurysms appeared to show a similarity in the global gene expression profile. Our results support the notion that disrupted homeostasis of the extracellular matrix components may be involved in the pathogenesis of intracranial aneurysms. Our data of the differentially regulated genes may benefit future studies on the cellular mechanisms of cerebral aneurysms.