Neurosurgery Department, Catholic University School of Medicine, Rome, Italy.
J Biol Regul Homeost Agents. 2013 Jul-Sep;27(3):729-38.
We tried to identify molecular markers in peripheral blood to predict high risk of aneurysm rupture. Extraction of the total population of peripheral blood mononuclear cell (PBMC) from total blood volume, total RNA extraction from PBMC and Agilent One Color Gene-expression Oligo-Microarray were performed on peripheral venous blood samples from 45 patients with ruptured, unruptured cerebral aneurysms and control group (15). Mean foreground/ background signal intensities and A (log2(R*G)/2) values were calculated for each spot. Genes with absolute fold change (FC) greater than or equal to plus or minus 1.5 and p-value less than 0.05 were considered differentially expressed in the 3 groups (Student T-test). Genes coding for MMPs were strongly underexpressed in ruptured aneurysms group, suggesting a possible role in aneurysms development more than their rupture. Genes coding for adhesine proteins of the extracellular matrix (ICAM1) and cytoskeleton (WIPF1,TUBA4A) were underexpressed in ruptured aneurysms. Genes coding proteins involved in the regulation of apoptotic processes may be important in aneurysm development and rupture, resulting into an increased rate of remodeling processes in the arterial wall. Fas coding gene, SUMO1, ZFAT, BCL2, CCR5 genes were all over-represented in unruptured aneurysms. The coexisting over-representation of pro-apoptotic genes and the underexpression of cytoskeleton and extracellular matrix genes confirms that aneurysms development and evolution are part of a degenerative process of the arterial wall not involved in aneurysms rupture. MMPs may be involved in repairing chronic damages to the arterial walls and preventing SAH. Unexpectedly, Heat Shock Proteins (HSP90AA1, HSPA1A, HSPB1), G and RAS proteins, generally activated by stress situations were under-represented in aneurysmal walls. Further PCR and Western Blotting studies are needed to confirm such findings and to identify diagnostic and prognostic markers in order to define screening protocols for intracranial aneurysms.
我们试图确定外周血中的分子标志物，以预测动脉瘤破裂的高危风险。从破裂、未破裂的脑动脉瘤患者和对照组（每组 15 例）的外周静脉血样本中提取全血总量的外周血单个核细胞（PBMC），并从 PBMC 中提取总 RNA，采用 Agilent One Color Gene-expression Oligo-Microarray 进行实验。计算每个点的平均前景/背景信号强度和 A（log2（R*G）/2）值。将差异表达的基因定义为倍数变化（FC）绝对值大于等于 1.5 倍且 p 值小于 0.05 的基因（Student T 检验）。MMPs 编码基因在外周血中的表达在破裂组中明显下调，提示其在动脉瘤形成中的作用可能大于破裂。细胞外基质（ICAM1）和细胞骨架（WIPF1，TUBA4A）黏附蛋白编码基因在外周血中的表达下调。参与凋亡过程调节的基因可能在动脉瘤形成和破裂中起重要作用，导致动脉壁重塑过程增加。Fas 编码基因、SUMO1、ZFAT、BCL2、CCR5 基因在外周血中的表达均上调。促凋亡基因的共存上调和细胞骨架及细胞外基质基因的下调证实，动脉瘤的形成和演变是动脉壁退行性过程的一部分，不涉及动脉瘤破裂。MMPs 可能参与修复动脉壁的慢性损伤，预防蛛网膜下腔出血。出乎意料的是，热休克蛋白（HSP90AA1、HSPA1A、HSPB1）、G 和 RAS 蛋白在外周血中的表达下调。需要进一步的 PCR 和 Western Blotting 研究来证实这些发现，并确定诊断和预后标志物，以便定义颅内动脉瘤的筛查方案。
