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Gene expression analysis shows the involvement of antigen presenting cells in intracranial aneurysm formation
Genexpressionsanalysen weisen auf die Beteiligung von Antigen-präsentierende Zellen bei der Formation intrakranieller Aneurysmen hin
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Veröffentlicht: | 30. Mai 2008 |
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Objective: To study the molecular processes involved in intracranial aneurysm formation, a gene expression analysis of a set of three different tissue samples was performed.
Methods: Using a dye swap technique, tissue samples of six ruptured and four unruptured aneurysms, as well as four intracerebral arteries serving as controls, were profiled using oligonucleotide microarrays. Differentially expressed genes were extracted comparing the expression ratio between the aneurysm and control tissue. Subsequently they were grouped according to the gene ontology classification. Focussing on the differentially expressed genes, a computational pathway analysis tool identified specific regulatory networks and pathways that may play a role in intracranial aneurysm formation. As a control we performed RT-PCR and immunohistochemical studies.
Results: Analysis of aneurysmal and control tissue revealed 521 differentially expressed genes. The most significantly associated gene ontology term was antigen processing (P=1.64E-16). Further network-based analysis showed the top scoring regulatory functional network to be built around overexpressed major histocompatibility class (MHC) I and II complex related genes. The canonical pathway “Antigen Presentation”was to confirmed have the highest upregulation in IA tissue (P=7.3E-10). Real time RT-PCR showed significant overexpression of MHC class II genes. Immunohistochemical staining showed strong positivity for MHC II molecule specific antibody (HLA II), for CD68 (macrophages, monocytes), for CD45RO (T-cells) and HLA I antibody.
Conclusions: Our results offer strong evidence for MHC class II gene overexpression in intracranial aneurysm tissue and for the fact that antigen presenting cells (macrophages, monocytes) play a key role in intracranial aneurysm formation.