Gene expression profiles in human ruptured and unruptured intracranial aneurysms: what is the role of inflammation?
OBJECTIVE
Mechanisms underlying development and rupture of intracranial aneurysms (IA) are poorly recognized. The majority of studies on human tissue have focused on predefined pathways. We sought to analyze global gene expression patterns of ruptured IA, unruptured IA, and control vessels.


METHODS
Transcription profiles were studied in human ruptured (n=8) and unruptured (n=6) IA, as well as in control intracranial arteries (n=5), using oligonucleotide microarrays. Real-time reverse-transcription polymerase chain reaction was used for confirmation. Functional analysis for determination of over-represented ontological groups among gene expression profiles was also performed.


RESULTS
The expression of 159 genes differed among the studied groups. Compared to the controls, 131 genes showed common directions of change in both IA groups. The most impacted biological processes for IA are: (1) the muscle system; (2) cell adhesion (downregulation); and (3) the immune system and inflammatory response (upregulation). Ruptured and unruptured IA differed in genes involved in immune/inflammatory processes; expression was reduced in ruptured IA.


CONCLUSIONS
Decreased expression of genes related to muscle system and cell adhesion is important for the development of IA. The role of immune/inflammatory processes is unclear. Inflammation may participate in the healing process within IA while playing a protective role against IA rupture.
Pera
Joanna
J
Department of Neurology, Jagiellonian University, Krakow, Poland. pera@su.krakow.pl
Korostynski
Michal
M
Krzyszkowski
Tadeusz
T
Czopek
Jacek
J
Slowik
Agnieszka
A
Dziedzic
Tomasz
T
Piechota
Marcin
M
Stachura
Krzysztof
K
Moskala
Marek
M
Przewlocki
Ryszard
R
Szczudlik
Andrzej
A
D000328:Adult; D000368:Aged; D002448:Cell Adhesion / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007107:Immune System / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D002532:Intracranial Aneurysm / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000503:physiopathology; D020411:Oligonucleotide Array Sequence Analysis; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013345:Subarachnoid Hemorrhage / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology
D005819:Genetic Markers