Transcriptome-Wide Characterization of Gene Expression Associated with Unruptured Intracranial Aneurysms

Abstract

Background: 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. Methods: 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. 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. Conclusion: 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.

DNA Methylation Regulates Gene Expression in Intracranial Aneurysms

“…As DNA methylation is a common epigenetic modification and an important regulator of gene expression, we aimed to investigate whether gene methylation modification affected the gene expression profiles in intracranial aneurysms. 16 We used microarrays to compare the methylation levels and gene expression profiles in tissue samples from intracranial aneurysms with matched tissue samples from the superficial temporal artery. The study investigate methylation modification as a potential mechanism for the observed gene expression changes in intracranial aneurysms.…”

Analysis of gene expression in intracranial aneurysms

“…In recent years, more and more high throughput methods were used to screen the pathogenic gene of intracranial aneurysm [10]. Lots of studies on whole genome sequencing of single nucleotide polymorphism (SNP) demonstrated different single nucleotide polymorphism loci may participate in the formation, development and rupture of intracranial aneurysms.…”

Screening of key genes of unruptured intracranial aneurysms by using DNA microarray data analysis techniques

“…The gene chip GSE26969 was downloaded from the gene expression database Gene Expression Omnibus (GEO) (Li et al, 2009), which contained data from six intracranial arterial tissue samples formed by three normal samples and three UIAs [GPL570 (HG-U133_ Plus_2) platform with Affymetrix HU133 Plus 2.0 microarrays]. Annotation information of the chip probe was performed using Affymetrix, which contained the complete Affymetrix ATH1 (25K) chip probe.…”

“…Several high-throughput screening approaches for understanding the genetics of unruptured intracranial aneurysms (UIAs) have been conducted in recent years (Li et al, 2009). However, high-throughput screening studies that focus on functional identification of differential gene expression are rare.…”