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

Abstract

ObjectiveSPARC 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.MethodsThirty-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.ResultsThe 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.ConclusionThe 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.

RNF213 Is Associated with Intracranial Aneurysms in the French-Canadian Population

“…Actually, the increased angiogenic activity might be a characteristic of the formation of aneurysm lesions, 68 and some studies have suggested high expression of angiogenic factors in IA tissues. 69,70 Another paper also stated that the ATP concentration is lower in aneurysm walls than in normal artery tissue. 71 We hypothesize that increased ATPase activity of RNF213 could lead to an increased or unbalanced level of angiogenesis and therefore be associated with the formation of aneurysmal lesions.…”

Integrative genomic analyses of secreted protein acidic and rich in cysteine and its role in cancer prediction

“…Matrix metalloproteinases (MMP-2, -3, -7 and -13), plasmin and trypsin, have been demonstrated to cleave SPARC in vitro, producing a KGHK-containing fragment (15,55,(56)(57)(58). The presence of the truncated form of the SPARC protein has been reported in hepatocellular carcinoma samples (59,60) and esophageal carcinoma (61).…”

Association of functional MMP-2 gene variant with intracranial aneurysms: case-control genetic association study and meta-analysis

“…7 8-12 MMPs are released by vascular endothelial, smooth muscle and inflammatory cells, 13 while increased expression of MMP-2 and 9 activity have been consistently shown within the walls of IAs, 7,[9][10][11][12]14 with upregulation of MMP-2 in ruptured IA. 11,12,15,16 The matrix metalloproteinase (MMP) -2 rs243865 C>T single nucleotide polymorphism (SNP) is of interest because it can influence transcription factor Sp1 (Specificity protein), thereby regulating the specificity and level of MMP-2 gene transcription. 17 Previous studies on this SNP in different populations have given inconclusive results 13,18 .…”