Increased expression of serum Matrix Metalloproteinase-9 in patients with moyamoya disease.
BACKGROUND
Moyamoya disease is a chronic occlusive cerebrovascular disease with unknown etiology characterized by an abnormal vascular network at the base of the brain, which can manifest both as ischemic stroke and as cerebral hemorrhage. It was also reported that the patients with moyamoya disease are more vulnerable to cerebral hyperperfusion such as postoperative hemorrhagic complication after extracranial-intracranial bypass surgery despite its low flow revascularization. However, the underlying mechanisms of its pathologic angiogenesis and the occurrence of hemorrhage are undetermined. Excessive degradation of the vascular matrix by MMPs, proteolytic enzymes that degrade all the components of extracellular matrix, can lead to instability of the vascular structure and can thereby cause bleeding. The MMPs also play an important role in tissue remodeling including angiogenesis in both physiologic and pathologic condition.


METHODS
We examined the serum levels of MMP-2 and MMP-9 in 16 cases with definitive moyamoya disease by enzyme-linked immunosorbent assay and compared them with those from healthy controls.


RESULTS
The serum MMP-9 level was significantly higher in moyamoya disease (40.18 ng/mL) than in healthy controls (13.75 ng/mL, P = .0372). There was no difference in serum MMP-2 level between moyamoya disease (646.65 ng/mL) and healthy control (677.60 ng/mL). Immunohistochemistry on the surgical specimens showed significant increase in MMP-9 expression within the arachnoid membrane of moyamoya disease.


CONCLUSIONS
The increased expression of MMP-9 may contribute to pathologic angiogenesis and/or to the instability of the vascular structure and could thereby cause hemorrhage in moyamoya disease.
Fujimura
Miki
M
Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan. fujimur@nsg.med.tohoku.ac.jp
Watanabe
Mika
M
Narisawa
Ayumi
A
Shimizu
Hiroaki
H
Tominaga
Teiji
T
D000293:Adolescent; D000328:Adult; D001099:Arachnoid / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000201:enzymology* / Q000503:physiopathology; D001929:Brain Edema / Q000097:blood / Q000201:enzymology* / Q000503:physiopathology; D002536:Cerebral Arteries / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D002543:Cerebral Hemorrhage / Q000201:enzymology* / Q000209:etiology / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D002648:Child; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000097:blood*; D008875:Middle Aged; D009072:Moyamoya Disease / Q000097:blood / Q000150:complications / Q000201:enzymology*; D009389:Neovascularization, Pathologic / Q000097:blood / Q000201:enzymology* / Q000209:etiology; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D015854:Up-Regulation / Q000502:physiology; D055815:Young Adult
D015415:Biomarkers; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9