Expression of osteopontin, matrix metalloproteinase-2 and -9 proteins in vascular instability in brain arteriovenous malformation

Lalita Anbarasen; Jasmine Lim; Retnagowri Rajandram; Kein Seong Mun; Sheau Fung Sia

doi:10.7717/peerj.7058

Expression of osteopontin, matrix metalloproteinase-2 and -9 proteins in vascular instability in brain arteriovenous malformation

PeerJ. 2019 Jun 24:7:e7058. doi: 10.7717/peerj.7058. eCollection 2019.

Authors

Lalita Anbarasen¹, Jasmine Lim¹, Retnagowri Rajandram¹, Kein Seong Mun², Sheau Fung Sia¹

Affiliations

¹ Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Wilayah Persekutuan Kuala Lumpur, Malaysia.
² Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Wilayah Persekutuan Kuala Lumpur, Malaysia.

Abstract

Background: Matrix 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.

Methodology: Serum 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.

Result: MMP-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.

Conclusion: Findings 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.

Keywords: Arteriovenous malformation; ELISA assay; Immunohistochemistry; Inflammatory markers; Intracranial hemorrhage.

Grants and funding

This work was supported by Fundamental Research Grant Scheme (FRGS) (FP019-2013B, J.L). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.