Fujimura Miki, Watanabe Mika, Narisawa Ayumi, Shimizu Hiroaki, Tominaga Teiji
Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
Surg Neurol. 2009 Nov;72(5):476-80; discussion 480. doi: 10.1016/j.surneu.2008.10.009. Epub 2009 Jan 14.
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.
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.
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.
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.
烟雾病是一种病因不明的慢性闭塞性脑血管疾病，其特征是脑底部出现异常血管网，可表现为缺血性卒中或脑出血。也有报道称，烟雾病患者更容易发生脑过度灌注，如颅外-颅内旁路手术后的术后出血并发症，尽管其血运重建流量较低。然而，其病理性血管生成和出血发生的潜在机制尚不清楚。基质金属蛋白酶（MMPs）是一种能降解细胞外基质所有成分的蛋白水解酶，其对血管基质的过度降解可导致血管结构不稳定，进而引起出血。MMPs在包括生理和病理状态下的血管生成在内的组织重塑中也发挥着重要作用。
我们通过酶联免疫吸附测定法检测了16例确诊烟雾病患者的血清MMP-2和MMP-9水平，并与健康对照者的水平进行比较。
烟雾病患者的血清MMP-9水平（40.18 ng/mL）显著高于健康对照者（13.75 ng/mL，P = 0.0372）。烟雾病患者（646.65 ng/mL）与健康对照者（677.60 ng/mL）的血清MMP-2水平无差异。手术标本的免疫组织化学显示，烟雾病蛛网膜内MMP-9表达显著增加。
MMP-9表达增加可能导致烟雾病的病理性血管生成和/或血管结构不稳定，从而引起出血。
