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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
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, Volume 68, No. 6, Year 2011
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Description
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.
Authors & Co-Authors
Kurki, Mitja Ilari
Finland, Kuopio
Itä-suomen Yliopisto
Frösen, Juhana K.
Finland, Kuopio
Kuopio University Hospital
von und zu Fraunberg, Mikael
Finland, Helsinki
Helsinki University Hospital
Tromp, Gerard C.
United States, Detroit
Wayne State University
United States
Geisinger Health System
Niemelä, Mika R.
Finland, Helsinki
Helsinki University Hospital
Jääskeläinen, Juha Erik
Finland, Kuopio
Kuopio University Hospital
Ylä-Herttuala, Seppo
Finland, Kuopio
Itä-suomen Yliopisto
Statistics
Citations: 118
Authors: 7
Affiliations: 5
Identifiers
Doi:
10.1227/NEU.0b013e318210f001
ISSN:
0148396X
Research Areas
Cancer
Genetics And Genomics
Noncommunicable Diseases
Study Design
Cross Sectional Study