The Expression of SPARC in Human Intracranial Aneurysms and Its Relationship with MMP-2/-9

OBJECTIVE 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. METHODS 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. RESULTS 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. CONCLUSION 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.