Sasaki Toshiyuki    Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine    Position   Assistant Professor
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Network-based gene expression analysis of intracranial aneurysm tissue reveals role of antigen presenting cells.
Journal	Formal name：Neuroscience Abbreviation：Neuroscience ISSN code：1873-7544(Electronic)0306-4522(Linking)
Volume, Issue, Page	154(4),pp.1398-407
Author and coauthor	Krischek B, Kasuya H, Tajima A, Akagawa H, Sasaki T, Yoneyama T, Ujiie H, Kubo O, Bonin M, Takakura K, Hori T, Inoue I
Publication date	2008/07
Summary	Little is known about the pathology and pathogenesis of the rupture of intracranial aneurysms. For a better understanding of the molecular processes involved in intracranial aneurysm (IA) formation we performed a gene expression analysis comparing ruptured and unruptured aneurysm tissue to a control artery. Tissue samples of six ruptured and four unruptured aneurysms, and four cerebral arteries serving as controls, were profiled using oligonucleotide microarrays. Gene ontology classification of the differentially expressed genes was analyzed and regulatory functional networks and canonical pathways were identified with a network-based computational pathway analysis tool. Real time reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical staining were performed as confirmation. 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 and confirmed the canonical pathway"Antigen Presentation"to 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. Our results offer strong evidence for MHC class II gene overexpression in human IA tissue and that antigen presenting cells (macrophages, monocytes) play a key role in IA formation.
DOI	10.1016/j.neuroscience.2008.04.049
Document No.	18538937