Circulating matrix metalloproteinases and their inhibitors in patients with Kawasaki disease (Retracted article. See vol. 125, pg. E1020, 2012)
Circulating matrix metalloproteinases and their inhibitors in patients with Kawasaki disease (Retracted article. See vol. 125, pg. E1020, 2012)
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DOI：
10.1161/hc3301.095286
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发表时间：
2001-08-21
期刊：
影响因子：
37.8
通讯作者：
Yokote, Y
中科院分区：
文献类型：
--
作者：
Senzaki, H;Masutani, S;Yokote, Y
由基质金属蛋白酶（MMPs）活性增加和/或MMP和MMP的组织抑制剂（TIMP）之间的数量失衡引起的基质加速分解与几种病理状况有关。MMP和TIMP也可能参与川崎病冠状动脉壁的破坏和由此引起的冠状动脉病变。方法与结果：采用酶联免疫法测定57例川崎病无冠状动脉病变患者（1组）和8例川崎病合并冠状动脉病变患者（2组）血浆MMPs、中性粒细胞弹性蛋白酶和TIMPs水平。分别在静脉注射丙种球蛋白治疗前后和恢复期采集血样。伽玛球蛋白治疗前川崎病患者MMPs、中性粒细胞弹性蛋白酶和TIMPs水平显著高于18例年龄匹配的发热对照组和17例年龄匹配的发热对照组（P < 0.01）。更重要的是，2组患者球蛋白前MMP9水平和MMP9/TIMP2比值、球蛋白后MMP3水平和MMP3/TIMP1比值均显著高于1组（P < 0.05）。虽然温热病对照组的MMP水平显著高于无热病对照组，但温热病对照组和无热病对照组的MMP/TIMP比值具有可比性。结论：这些数据表明川崎病患者和高水平的MMP和/或MMP/TIMP易发生冠状动脉病变。MMP抑制剂对冠状动脉预后影响的研究可能提供证据，证明MMP是预防川崎病引起的冠状动脉病变的可行治疗靶点。
Background-Accelerated matrix breakdown caused by the increased activity of matrix metalloproteinases (MMPs) and/or the quantitative imbalance between MMP and tissue inhibitor of MMP (TIMP) have been implicated in several pathological conditions. MMP and TIMP may also be, involved in the destruction of the coronary arterial wall and the resultant coronary arterial lesions in Kawasaki disease.Methods and Results-Plasma levels of MMPs, neutrophil elastase, and TIMPs were measured by enzyme-linked immunoassay in 57 patients with Kawasaki disease and no coronary arterial lesions (group 1) and in 8 patients with Kawasaki disease and coronary arterial lesions (group 2). Blood samples were obtained before and after intravenous gamma globulin therapy and in the convalescent stage. Levels of MMPs, neutrophil elastase, and TIMPs were significantly higher in Kawasaki disease patients before gamma globulin therapy than in 18 age-matched afebrile control subjects and 17 age-matched febrile disease control subjects (P < 0.01). More importantly, the pre-gamma globulin MMP9 level and MMP9/TIMP2 ratio and post-gamma globulin MMP3 level and MMP3/TIMP1 ratio were significantly higher in group 2 than in group I patients (P < 0.05). Although MMP levels in febrile disease controls were significantly higher than those of afebrile controls, the MMP/TIMP ratios of febrile disease controls and afebrile controls were comparable.Conclusions-These data suggest that patients with Kawasaki disease and high levels of MMP and/or MMP/TIMP are susceptible to coronary arterial lesions. Studies of the effects of MMP inhibitors on coronary outcome may provide evidence that MMP is a viable therapeutic target for the prevention of coronary arterial lesions due to Kawasaki disease.