Gene Expression Profiles in Human Ruptured and Unruptured Intracranial Aneurysms: What Is the Role of Inflammation?

Background and Purpose— 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.

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