Expression of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) in cerebral cavernous malformations: immunohistochemical analysis of MMP-2, -9 and TIMP-2.
OBJECTIVE
Hemorrhage from cerebral vascular malformations such as cerebral cavernous malformation (CCM) can result in significant mortality and morbidity, but its underlying mechanism is undetermined. Excessive degradation of the vascular matrix by matrix metalloproteinases (MMPs), proteolytic enzymes that degrade all the components of extracellular matrix, can lead to instability of the vascular structure and can thereby cause bleeding. Thus we examined the expression of MMPs and tissue inhibitors of metalloproteinase (TIMP) in CCM.


METHODS
We performed immunohistochemistry for MMP-2, -9, and TIMP-2 using Paraffin-embedded sections of the surgical specimens obtained from seven patients with CCM. All patients had a history of hemorrhage from CCM.


RESULTS
In all patients (7/7, 100%), MMP-2 and -9 were strongly expressed in endothelial cells of CCMs. Endothelial expression of TIMP-2 was also evident in all seven patients. In contrast, MMP-2, -9 and TIMP-2 were not identified in adjacent normal brain tissue.


CONCLUSIONS
We found that CCM showed the increased endothelial expression of MMP-2, -9, and TIMP-2. Endothelial expression of MMPs and/or TIMP may affect the vascular matrix stability, and thus can contribute to hemorrhage from CCM.
Fujimura
M
M
Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan. fujimur@nsg.med.tohoku.ac.jp
Watanabe
M
M
Shimizu
H
H
Tominaga
T
T
D000328:Adult; D020785:Central Nervous System Vascular Malformations / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D002648:Child; D042783:Endothelial Cells / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D012307:Risk Factors; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*
D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9