Neuroradiology Research Laboratory, Department of Radiology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Neurosurgery. 2010 Mar;66(3):578-84; discussion 584. doi: 10.1227/01.NEU.0000365769.78334.8C.
Morphologic features are thought to play a critical role in the rupture of intracranial, saccular aneurysms.
The objective of this study was to investigate the gene expression pattern of saccular aneurysms with distinct morphologic patterns.
Elastase-induced saccular aneurysms with high (>or= 2.4) and low (<or= 1.6) aspect ratios (ARs) (height to neck width) were created in 15 rabbits (n = 9 for high AR and n = 6 for low AR). RNA was isolated from the aneurysms and analyzed using a microarray containing 294 rabbit genes of interest. Genes with a statistically significant difference between low and high AR (P < .05) and a fold change of >or= 1.5 and <or= 0.75 to represent up- and down-regulation in high AR compared with low AR were used to identify pathways for further investigation.
Fourteen genes (4.8%) were differentially expressed in high-AR aneurysms compared with low-AR aneurysms. The expression of osteopontin, tissue inhibitor of matrix metalloproteinase, haptoglobin, cathepsin L, collagen VIII, fibronectin, galectin 3, secreted frizzled-related protein 2, CD14, decorin, and annexin I were up-regulated, whereas the expression of myosin light chain kinase, Fas antigen, and CD34 were down-regulated in high-AR aneurysms.
In a rabbit model of saccular aneurysm, high AR was associated with differential expression of inflammatory/immunomodulatory genes, structural genes, genes related to proteolytic enzymes and extracellular matrix-related genes. These findings may focus efforts on targets aimed at avoiding spontaneous rupture of intracranial, saccular aneurysms.
形态特征被认为在颅内囊状动脉瘤破裂中起着关键作用。
本研究旨在探讨具有不同形态特征的囊状动脉瘤的基因表达模式。
在 15 只兔子中创建了弹性蛋白酶诱导的高（≥2.4）和低（≤1.6）形态比（高度与颈部宽度比）囊状动脉瘤（高形态比 n = 9，低形态比 n = 6）。从动脉瘤中分离 RNA，并使用包含 294 个感兴趣的兔基因的微阵列进行分析。在低形态比和高形态比之间具有统计学显著差异（P<.05）的基因，以及代表高形态比相对于低形态比上调或下调的倍数变化为>或= 1.5 和<或= 0.75 的基因，用于识别进一步研究的途径。
与低形态比动脉瘤相比，高形态比动脉瘤中有 14 个基因（4.8%）表达差异。骨桥蛋白、基质金属蛋白酶抑制剂、触珠蛋白、组织蛋白酶 L、VIII 型胶原、纤维连接蛋白、半乳糖凝集素 3、分泌卷曲相关蛋白 2、CD14、核心蛋白聚糖和膜联蛋白 I 的表达上调，而肌球蛋白轻链激酶、Fas 抗原和 CD34 的表达下调。
在兔囊状动脉瘤模型中，高形态比与炎症/免疫调节基因、结构基因、与蛋白水解酶和细胞外基质相关基因的差异表达相关。这些发现可能集中精力于旨在避免颅内囊状动脉瘤自发性破裂的目标。
