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 <0.01 and >2-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 P<0.01 and fold change >1.5. RESULTS: There are 326 distinct differentially expressed genes between IA and superficial temporal artery tissues (>2-fold change) with a false discovery rate <0.01. 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.
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 <0.01 and >2-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 P<0.01 and fold change >1.5. RESULTS: There are 326 distinct differentially expressed genes between IA and superficial temporal artery tissues (>2-fold change) with a false discovery rate <0.01. 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.
Authors: Timo Krings; Daniel M Mandell; Tim-Rasmus Kiehl; Sasikhan Geibprasert; Michael Tymianski; Hortensia Alvarez; Karel G terBrugge; Franz-Josef Hans Journal: Nat Rev Neurol Date: 2011-09-20 Impact factor: 42.937
Authors: Riikka Tulamo; Juhana Frösen; Anders Paetau; Sanna Seitsonen; Juha Hernesniemi; Mika Niemelä; Irma Järvelä; Seppo Meri Journal: Am J Pathol Date: 2010-10-22 Impact factor: 4.307
Authors: Kimon Bekelis; Joanna S Kerley-Hamilton; Amy Teegarden; Craig R Tomlinson; Rachael Kuintzle; Nathan Simmons; Robert J Singer; David W Roberts; Manolis Kellis; David A Hendrix Journal: J Neurosurg Date: 2016-02-26 Impact factor: 5.115
Authors: David M Hasan; Nohra Chalouhi; Pascal Jabbour; Vincent A Magnotta; David K Kung; William L Young Journal: J Neuroradiol Date: 2013-02-18 Impact factor: 3.447
Authors: Robert M Starke; Nohra Chalouhi; Muhammad S Ali; Pascal M Jabbour; Stavropoula I Tjoumakaris; L Fernando Gonzalez; Robert H Rosenwasser; Walter J Koch; Aaron S Dumont Journal: Curr Neurovasc Res Date: 2013-08 Impact factor: 1.990