Although significant advances have been made towards a better understanding of intracranial aneurysm natural history, there still are more questions than answers. Why certain aneurysms remain quiescent while others grow and rupture remains largely unpredictable. A better understanding of biological processes in the aneurysm wall may shed light on mechanisms of aneurysm formation, growth and rupture. To this end, Pera et al (Stroke. 2010;41:224–231) analyzed the gene expression patterns in the walls of ruptured aneurysms (RIA), unruptured aneurysms (UIA) and control vessels, with a focus on inflammatory processes.
The authors prospectively collected 8 RIA and 6 UIA domes and 5 middle meningeal artery (MMA) segments as control intracranial arteries. After RNA isolation, microarray analysis was performed. Results of differentially expressed genes were validated with real-time reverse-transcription polymerase chain reaction.
When comparing all aneurysms to control vessels, 159 differentially expressed genes were identified. Of these genes, 131 were common for ruptured and unruptured aneurysms (8 upregulated, 123 downregulated). Twenty six were specific for UIA and were upregulated; 2 were specific for RIA and were downregulated. When comparing UIA and RIA, 32 differentially expressed genes were found. Of these genes, 28 were also differentially expressed when all aneurysms were compared to control vessels. Analysis of the differentially expressed genes between all aneurysms and MMA revealed that the most represented gene categories were: 1) Inflammatory/immune related genes—upregulated; 2) Muscle system related genes—downregulated; 3) Cell adhesion related genes—downregulated; 4) cell membrane related genes—downregulated. When comparing UIA and RIA groups the same categories accounted for the differential expression. Histological examination of aneurysm walls revealed inflammatory cell infiltration whereas these cells were absent in control vessels.
Inflammatory and immune processes have been implicated in aneurysm pathobiology. The role these processes play in aneurysm formation, growth and rupture, however, have not been elucidated. The increased expression of inflammatory related genes in unruptured aneurysms in this study raises questions as to whether inflammation is protective from or conducive to aneurysm rupture. A better understanding of whether and how inflammation modulates aneurysm behavior, may open avenues to better disease prediction, more refined population screening and targeted biological therapies.
RUDY J. RAHME
BERNARD R. BENDOK