The expression of SPARC in human intracranial aneurysms and its relationship with MMP-2/-9.

SPARC is a key determinant of invasion and metastasis in some tumors, such as gliomas, melanomas and prostate tumors. SPARC can change the composition and structure of the matrix and promote angiogenesis; these effects are closely related to clinical stage and the prognosis of tumors such as meningiomas. However, little is known about the expression of SPARC in intracranial aneurysms. The goal of this study was to establish the role of SPARC in human intracranial aneurysms. Thirty-one intracranial aneurysms were immunohistochemically stained for SPARC, MMP-2 and MMP-9. As controls, normal Circle of Willis arteries were similarly immunostained. All specimens were retrieved during autopsies and were embedded in paraffin. To evaluate the expression levels of SPARC, MMP-2 and MMP-9, western blotting was also performed in three available intracranial aneurysm specimens. The limited availability of fresh intracranial aneurysm tissue was the result of the majority of patients choosing endovascular embolization. The results showed that SPARC, MMP-2 and MMP-9 were strongly expressed in intracranial aneurysm tissues; however, these proteins were expressed minimally or not at all in normal Circle of Willis arteries. The western blot results showed that the expression levels of SPARC, MMP-2 and MMP-9 were significantly up-regulated in intracranial aneurysms relative to the expression levels in the normal Circle of Willis arteries. Data analysis showed that SPARC was significantly correlated with MMP-2 and MMP-9, also with age and risk factors but not with the Hunt-Hess grade or with sex. The results indicate that SPARC is widely expressed in human intracranial aneurysms, and its expression correlates with MMP-2 and MMP-9 expression, age and risk factors but not with the Hunt-Hess grade. The results of this study suggest that SPARC has a pathogenic role in the alteration of the extracellular matrix of intracranial arteries during aneurysm formation.

SPARC是一些肿瘤（如神经胶质瘤、黑色素瘤和前列腺肿瘤）侵袭和转移的关键决定因素。SPARC能够改变基质的组成和结构并促进血管生成；这些作用与脑膜瘤等肿瘤的临床分期和预后密切相关。然而，关于SPARC在颅内动脉瘤中的表达知之甚少。本研究的目的是确定SPARC在人颅内动脉瘤中的作用。 对31个颅内动脉瘤进行SPARC、MMP - 2和MMP - 9的免疫组织化学染色。作为对照，对正常的Willis环动脉进行类似的免疫染色。所有标本均在尸检时获取并包埋在石蜡中。为了评估SPARC、MMP - 2和MMP - 9的表达水平，还对3个可用的颅内动脉瘤标本进行了蛋白质印迹分析。新鲜颅内动脉瘤组织有限的原因是大多数患者选择血管内栓塞治疗。 结果显示，SPARC、MMP - 2和MMP - 9在颅内动脉瘤组织中强烈表达；然而，这些蛋白质在正常的Willis环动脉中极少表达或根本不表达。蛋白质印迹结果显示，与正常Willis环动脉中的表达水平相比，SPARC、MMP - 2和MMP - 9在颅内动脉瘤中的表达水平显著上调。数据分析显示，SPARC与MMP - 2和MMP - 9显著相关，也与年龄和危险因素相关，但与Hunt - Hess分级或性别无关。 结果表明，SPARC在人颅内动脉瘤中广泛表达，其表达与MMP - 2和MMP - 9的表达、年龄和危险因素相关，但与Hunt - Hess分级无关。本研究结果提示，SPARC在动脉瘤形成过程中对颅内动脉细胞外基质的改变具有致病作用。