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The expression of SPARC in human intracranial aneurysms and its relationship with MMP-2/-9
1Department of Neurosurgery, Qilu Hospital, Shandong University, Jinan, People's Republic of China. libo5479937@yahoo.cn
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.
Insights
Secreted protein acidic and rich in cysteine (SPARC) is highly expressed in brain aneurysms, correlating with matrix-degrading enzymes and patient age. This suggests SPARC plays a role in aneurysm development.
Area of Science:
- Neuroscience
- Vascular Biology
- Oncology
Background:
- Secreted protein acidic and rich in cysteine (SPARC) influences extracellular matrix composition and angiogenesis, impacting tumor progression.
- SPARC's role in tumors like gliomas and melanomas is established, but its function in intracranial aneurysms remains unclear.
Purpose of the Study:
- To investigate the expression and role of SPARC in human intracranial aneurysms.
Main Methods:
- Immunohistochemical staining of 31 intracranial aneurysms and normal Circle of Willis arteries for SPARC, MMP-2, and MMP-9.
- Western blotting to quantify protein expression levels in available aneurysm specimens.
Main Results:
- SPARC, MMP-2, and MMP-9 were significantly upregulated in intracranial aneurysms compared to normal arteries.
- SPARC expression correlated with MMP-2, MMP-9, age, and risk factors, but not Hunt-Hess grade or sex.
Conclusions:
- SPARC is widely expressed in intracranial aneurysms and is associated with matrix metalloproteinase activity.
- These findings suggest SPARC contributes to extracellular matrix alterations in intracranial aneurysms, indicating a potential pathogenic role.
