Proteomic identification of differentially expressed proteins in vascular wall of patients with ruptured intracranial aneurysms

Objective: Intracranial aneurysms (IA) are serious cerebral vascular abnormalities, however, little is known about the mechanisms underlying IA formation, progression and rupture. Therefore, this study aimed to assess protein expression specific to the vascular tissues of IA patients. Methods: IA samples were intraoperatively collected from 14 patients after microneurosurgical clipping and pooled. Matched superficial temporal artery (STA) tissues collected from the same patients were used as controls. Differentially expressed proteins were identified using isobaric tags for relative and absolute quantification (iTRAQ) and two-dimensional liquid chromatography-tandem mass spectrometry (2D LC-MS/MS), validated by immunoblot. Results: 816 proteins were found to be differently expressed in IA and healthy tissues. The expression level of 162 proteins differed by at least two fold. Expression of 80 proteins was up-regulated and expression of 82 was down-regulated. According to PANTHER, these proteins were involved in immune responses, cell adhesion, cellular component organization and developmental processes. Azurocidin-1 (AZU1, a known antimicrobial) and Transmembrane 9 superfamily member 1 (TM9SF1, a novel autophagy-related protein) were 8.0 and 8.6 fold up-regulated, respectively, in IA, while Sorbin and SH3 domain-containing protein 2 (SORBS2), involved in signaling complex assembly, was 12.1 fold down-regulated. Conclusion: These findings suggest that IA formation and rupture might be related to autophagy and immune responses, which possibly accounts for proteolytic degradation of vessel wall connective tissues and cytoskeleton components.