Wang Chengdong, Qu Bingkun, Wang Zhe, Ju Jiyu, Wang Yuting, Wang Zengwu, Cao Peicheng, Wang Daokui
The Central Laboratory, Weifang People's Hospital, No. 151 Guangwen Road, Weifang 261041, Shandong, China.
Department of Neurosurgery, Weifang People's Hospital, No. 151 Guangwen Road, Weifang 261041, Shandong, China.
Atherosclerosis. 2015 Feb;238(2):201-6. doi: 10.1016/j.atherosclerosis.2014.11.027. Epub 2014 Dec 2.
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.
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.
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.
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.
颅内动脉瘤（IA）是严重的脑血管异常疾病，然而，关于IA形成、进展和破裂的潜在机制知之甚少。因此，本研究旨在评估IA患者血管组织特有的蛋白质表达。
在显微神经外科夹闭术后，从14例患者术中采集IA样本并合并。从同一患者采集的匹配颞浅动脉（STA）组织用作对照。使用相对和绝对定量等压标签（iTRAQ）和二维液相色谱 - 串联质谱（2D LC-MS/MS）鉴定差异表达的蛋白质，并通过免疫印迹进行验证。
发现816种蛋白质在IA组织和健康组织中差异表达。162种蛋白质的表达水平差异至少两倍。80种蛋白质表达上调，82种蛋白质表达下调。根据PANTHER分类系统，这些蛋白质参与免疫反应、细胞粘附、细胞成分组织和发育过程。天青杀素 -1（AZU1，一种已知的抗菌蛋白）和跨膜9超家族成员1（TM9SF1，一种新型自噬相关蛋白）在IA中分别上调8.0倍和8.6倍，而参与信号复合物组装的含Sorbin和SH3结构域蛋白2（SORBS2）下调12.1倍。
这些发现表明，IA的形成和破裂可能与自噬和免疫反应有关，这可能解释了血管壁结缔组织和细胞骨架成分的蛋白水解降解。
