Comparison of gene expression between ruptured and unruptured human intracranial aneurysms

ABSTRACT: Background and Purpose Aneurysmal subarachnoid hemorrhage, almost always from saccular intracranial aneurysm (sIA), is a devastating form of stroke that affects working age population. Cellular and molecular mechanisms predisposing to the rupture of the sIA wall are largely unknown. Such knowledge would facilitate the design of novel diagnostic tools and therapies for the sIA disease. Methods We compared the whole genome expression profile of eleven ruptured sIA wall samples, resected at a median of 15 hours after rupture, to that of eight unruptured ones. 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 downregulated in the ruptured sIA walls. Significantly upregulated biological processes included: response to turbulent blood flow; chemotaxis; leukocyte migration; oxidative stress; vascular remodelling; and extracellular matrix degradation. Toll like receptor (TLR) signalling and NF-κB, HIF1A and ETS transcription factor binding sites were significantly enriched among the upregulated genes. Conclusions We identified pathways and candidate genes associated to the rupture of human sIA wall. These results provide a molecular basis analysis (a) to identify rupture-prone sIAs and (b) to prevent their rupture. Novel measures to prevent the rupture of sIA wall may include inhibition of response to turbulent blood flow, leukocyte migration, TLR signalling, or blockade of NF-κB, HIF1A and ETS transcription factors. Human aneurysm pouches were clipped intraoperatively and immediately snap frozen. RNA was extracted from 19 (11 ruptured and 8 unruptured) aneurysm samples and used in microarray hybridization.

SUBMITTER:  

PROVIDER: S-DIXA-D-1014 | biostudies-other |

REPOSITORIES: biostudies-other