Abstract
BackgroundMatrix metalloproteinase (MMP)-2 and -9 are Osteopontin (OPN) dependent molecules implicated in the destabilization of blood vessels. OPN and MMPs have been studied in brain arteriovenous malformation (BAVM) patients’ tissues and blood samples before intervention. In this study, we compared the serum level of these markers before and after treatment, as well as assessed their protein expressions in BAVM tissues to evaluate their roles in this disease.MethodologySerum samples from six BAVM patients and three control subjects were analyzed using enzyme-linked immunoabsorbent assay (ELISA) for OPN. A total of 10 BAVM patients and five control subjects were analyzed using Multiplex ELISA for MMPs. A total of 16 BAVM tissue samples and two normal brain tissue samples were analyzed using immunohistochemistry.ResultMMP-2 and -9 were significantly higher in the serum of BAVM patients before and after treatment than in control patients. There were no significant differences of OPN and MMP-9 serum level in BAVM patients before and after treatment. MMP-2 showed a significant elevation after the treatment. Expression of OPN, MMP-2 and -9 proteins were seen in endothelial cells, perivascular cells and brain parenchyma of BAVM tissues.ConclusionFindings revealed that the level of MMP-2 and -9 in the serum correlated well with the expression in BAVM tissues in several cases. Knockdown studies will be required to determine the relationships and mechanisms of action of these markers in the near future. In addition, studies will be required to investigate the expression of these markers’ potential applications as primary medical therapy targets for BAVM patients.
Highlights
The prevalence of brain arteriovenous malformation (BAVM) in the general population is approximately 0.001–0.52% (Solomon & Connolly, 2007)
Expression of Matrix metalloproteinase (MMP)-2 and -9 in serum of BAVM patients Expression of MMP-2 showed a significant difference in the serum sample of BAVM patients 24 h before and after treatment, with p-value of 0.011Ã (Wilcoxon signed rank test) (Fig. 1B)
This finding lends support to the postulation that these markers play a role in the weakening of vessel walls. Further analysis of these markers in tissue samples is required to study the pathogenesis of instability of vessel walls, perhaps in vitro experiments involving the knockdown of the expression of OPN, MMP-2 and -9. This preliminary study on the inflammatory markers involved in the destabilization of blood vessels showed the expression of OPN, MMP-2 and -9 in tissue samples of BAVM patients
Summary
The prevalence of brain arteriovenous malformation (BAVM) in the general population is approximately 0.001–0.52% (Solomon & Connolly, 2007). In this study we preliminarily analyzed the expression of these proteins in BAVM patients’ serum samples and compared with controls. We studied the expression of these markers in tissue samples to analyze the localization of the proteins This might help in predicting the risk of rupture. OPN and MMPs have been studied in brain arteriovenous malformation (BAVM) patients’ tissues and blood samples before intervention. We compared the serum level of these markers before and after treatment, as well as assessed their protein expressions in BAVM tissues to evaluate their roles in this disease. Methodology: Serum samples from six BAVM patients and three control subjects were analyzed using enzyme-linked immunoabsorbent assay (ELISA) for OPN. There were no significant differences of OPN and MMP-9 serum level in BAVM patients before and after treatment. Studies will be required to investigate the expression of these markers’ potential applications as primary medical therapy targets for BAVM patients
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