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Upregulated signaling pathways in ruptured human saccular intracranial aneurysm wall: An emerging regulative role of toll-like receptor signaling and nuclear factor-κB, hypoxia-inducible factor-1A, and ETS transcription factors
Kurki M.I.1; Hakkinen S.-K.1; Frosen J.5; Tulamo R.5; Von Und Zu Fraunberg M.3; Wong G.1; Tromp G.4; Niemela M.3; Hernesniemi J.3; Jaaskelainen J.E.5; Yla-Herttuala S.1
2011-06-01
Source PublicationNeurosurgery
ISSN0148396X
Volume68Issue:6Pages:1667-1675
Abstract

Background: Aneurysmal subarachnoid hemorrhage, almost always from saccular intracranial aneurysm (sIA), is a devastating form of stroke that affects the working-age population. Cellular and molecular mechanisms predisposing to the rupture of the sIA wall are largely unknown. This knowledge would facilitate the design of novel diagnostic tools and therapies for the sIA disease. Objective: To investigate gene expression patterns distinguishing ruptured and unruptured sIA. Methods: We compared the whole-genome expression profile of 11 ruptured sIA wall samples with that of 8 unruptured ones using oligonucleotide microarrays. Signaling pathways enriched in the ruptured sIA walls were identified with bioinformatic analyses. Their transcriptional control was predicted in silico by seeking the enrichment of conserved transcription factor binding sites in the promoter regions of differentially expressed genes. Results: Overall, 686 genes were significantly upregulated and 740 were downregulated in the ruptured sIA walls. Significantly upregulated biological processes included response to turbulent blood flow, chemotaxis, leukocyte migration, oxidative stress, vascular remodeling; and extracellular matrix degradation. Toll-like receptor signaling and nuclear factor-κB, hypoxia-inducible factor-1A, and ETS transcription factor binding sites were significantly enriched among the upregulated genes. Conclusion: We identified pathways and candidate genes associated with the rupture of human sIA wall. Our results may provide clues to the molecular mechanism in sIA wall rupture and insight for novel therapeutic strategies to prevent rupture. Copyright © 2011 by the Congress of Neurological Surgeons.

KeywordInflammation Microarray Analysis Saccular Aneurysm Subarachnoid Hemorrhage Transcription Factors
DOI10.1227/NEU.0b013e318210f001
URLView the original
Indexed BySCI
Language英语
WOS Research AreaNeurosciences & Neurology ; Surgery
WOS SubjectClinical Neurology ; Surgery
WOS IDWOS:000290299700073
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Cited Times [WOS]:60   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.Itä-Suomen yliopisto
2.Weis Center for Research
3.Helsinki University Hospital
4.Wayne State University
5.Kuopio University Hospital
Recommended Citation
GB/T 7714
Kurki M.I.,Hakkinen S.-K.,Frosen J.,et al. Upregulated signaling pathways in ruptured human saccular intracranial aneurysm wall: An emerging regulative role of toll-like receptor signaling and nuclear factor-κB, hypoxia-inducible factor-1A, and ETS transcription factors[J]. Neurosurgery,2011,68(6):1667-1675.
APA Kurki M.I..,Hakkinen S.-K..,Frosen J..,Tulamo R..,Von Und Zu Fraunberg M..,...&Yla-Herttuala S..(2011).Upregulated signaling pathways in ruptured human saccular intracranial aneurysm wall: An emerging regulative role of toll-like receptor signaling and nuclear factor-κB, hypoxia-inducible factor-1A, and ETS transcription factors.Neurosurgery,68(6),1667-1675.
MLA Kurki M.I.,et al."Upregulated signaling pathways in ruptured human saccular intracranial aneurysm wall: An emerging regulative role of toll-like receptor signaling and nuclear factor-κB, hypoxia-inducible factor-1A, and ETS transcription factors".Neurosurgery 68.6(2011):1667-1675.
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