Genomics of Human Intracranial Aneurysm Wall

Abstract

Background and Purpose-The pathogenesis of intracranial aneurysms (IAs) remains elusive. Most studies have focused on individual genes, or a few interrelated genes or products, at a time in human IA. However, a broad view of pathologic mechanisms has not been investigated by identifying pathogenic genes and their interaction in networks. Our study aimed to analyze global gene expression patterns in the IA wall. Methods-To our knowledge, our group was the first to perform Illumina microarray analysis on human IA via comparison of aneurysm wall and superficial temporal artery tissues from 6 consecutive patients. We adopted stringent statistical criteria to the individual genes; genes with a false discovery rate Ͻ0.01 and Ͼ2-fold change were selected as differentially expressed. To identify the overrepresented biologic pathways with the differentially expressed genes, we performed hypergeometric testing of the genes selected by relaxed criteria of PϽ0.01 and fold change Ͼ1.5. Results-There are 326 distinct differentially expressed genes between IA and superficial temporal artery tissues (Ͼ2-fold change) with a false discovery rate Ͻ0.01. Analysis of the Kyoto Encyclopedia of Genes and Genomes pathways revealed the most impacted functional pathways: focal adhesion, extracellular matrix receptor interaction, and cell communication. Analysis of the Gene Ontology also supported the involvement of another 2 potentially important pathways: inflammatory response and apoptosis. Conclusions-The differentially expressed genes in the aneurysm wall may shed light on aneurysm pathobiology and provide novel targets for therapeutic intervention. These data will help generate hypotheses for future studies. (Stroke.

Gene Expression Profiles in Human Ruptured and Unruptured Intracranial Aneurysms

“…The gene microarray method allows for simultaneous analysis of the expression of thousands of genes. We are aware of only 3 published studies [2][3][4] in which the microarray technique was used for profiling gene expression in human IA. In one study, samples were obtained from autopsies and were pooled.…”

Gene Expression Microarray Studies of Intracranial Aneurysm Walls Lead to Similar Results

“…Shi et al report to have found 6 functional annotation groups to have the most relevance in terms of aneurysm development and rupture: collagens, cell communication, angiogenesis, inflammation, apoptosis and cytoskeleton negative regulation. 1 In a previous serial analysis of gene expression comparing tissue of a single intracranial aneurysm compared with a matched superficial temporal artery, strong immune and inflammatory response was also detected. 3 A drawback of our study and rightful criticism of the reviewers at the time of submission was the use of arteriovenous malformation feeder tissue as a control.…”

“…1 Back in May 2008 we published our gene expression micorarray study results of 4 unruptured and 6 ruptured aneurysms, as well as 4 arteriovenous malformation feeders which were obtained in a similar way. 2 We used the same pathway analysis program "Ingenuity Pathway Analysis"; the microarray platform used was an Agilent Human Oligo Microarray which carries 18 716 transcripts of human gene expressions.…”

Advances in Stroke 2009

“…Bioinformatics pathway analysis revealed that many of these genes could be attributed to 1 of the following pathways: focal adhesion, extracellular matrix receptor interaction, and cell communication. 19 Yet, despite such progress, the critical players still need to be identified. Furthermore, the biology behind these altered expression profiles requires disentanglement.…”

“…В другом исследовании с учас-тием пациентов с аневризмами внутричерепных сосудов обнаружили 326 генов, экспрессия которых проходила избирательно по сравнению с экспресси-ей в неповрежденных артериях у тех же пациентов. Биоинформационный анализ показал, что многие из этих генов участвуют в одном из следующих про-цессов: фокальной адгезии, взаимодействии рецеп-торов внеклеточного матрикса и установлении меж-клеточных связей [19]. Однако, несмотря на достиг-нутый прогресс, еще предстоит выявить ключевые звенья этих процессов.…”