Gene Expression Profiles in Human Ruptured and Unruptured Intracranial Aneurysms

Abstract

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 (nϭ8) and unruptured (nϭ6) IA, as well as in control intracranial arteries (nϭ5), 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.

α5 and αv integrins cooperate to regulate vascular smooth muscle and neural crest functions in vivo

“…Alternatively, these regions might be more susceptible, due to being populated by different subsets of CNCCs, compared with other parts of the great vessels, and heightened expression of β1 integrins might simply correlate with a specific population of vSMCs. Interestingly, decreased expression of ITGA5 has previously been linked to formation of human aortic aneurysms (Cheuk and Cheng, 2004), and, similar to some human aneurysms (Pera et al, 2010) and experimentally induced aneurysms in mice (Murphy and Hynes, 2014), Pecam1-positive endothelial cells were reduced in the dilated brachiocephalic artery of Itga5/av SM22-Cre mice at late stages. It is unclear, however, whether this loss is specifically linked to deletion of both α5 and αv within vSMCs, or merely part of the general pathology occurring within a large aneurysm.…”

Biology of Intracranial Aneurysms: Role of Inflammation

“…In addition, degenerative changes are seen within medial SMC (Hazama and Hashimoto, 1987). Upon closer inspection, an early event involves VSMC undergoing phenotypic modulation from differentiated SMC concerned with contraction (characterized by the significant expression of contractile genes/proteins such as smooth muscle-myosin heavy chain, and smooth musclea-actin) to cells with a pro-inflammatory, pro-matrix remodeling phenotype characterized by the increased expression of inflammatory factors and MMP (Figure 1; Supplementary Figure 1) (Aoki et al, 2007b(Aoki et al, , 2010Ishibashi et al, 2010;Kilic et al, 2005;Kolega et al, 2011;Merei and Gallyas, 1980;Nakajima et al, 2000;Pera et al, 2010;Sakaki et al, 1997;Sibon et al, 2008;Tada et al, 2011). Phenotypic modulation of VSMC was an early morphological observation in some IA walls where spindlelike VSMC, arranged in a parallel manner, may dissociate from each other to be transformed into spiderlike cells (Merei and Gallyas, 1980).…”

“…In a well-designed microarray study, Pera et al (2010) examined transcription profiles in ruptured (n = 6) and unruptured (n = 4) IA compared with control middle meningeal arteries. There were changes in expression of 159 genes compared with control with 131 genes showing common directions of change in both ruptured and unruptured IA.…”

Transcriptome network-based method to identify genes associated with unruptured intracranial aneurysms

“…The RING motif is a cysteine-rich sequence found in a variety of proteins that regulate cell growth, including the products of tumor suppressor genes and dominant protooncogenes. BARD1 has been found to be downregulated in IA (Pera et al, 2010).…”