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Elevated Levels of Matrix Metalloproteinase 9 and Tissue Inhibitor of Metalloproteinase 1 during the Acute Phase of Kawasaki Disease

机译:川崎病急性期基质金属蛋白酶9和金属蛋白酶1组织抑制剂的水平升高

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Kawasaki disease (KD) is an acute, self-limiting, multisystem vasculitis of unknown etiology affecting infants and young children. Unless treated promptly with high-dose intravenous gamma globulin and aspirin, patients frequently develop coronary aneurysms. Previously, matrix metalloproteinase 9 (MMP-9), which is secreted complexed to tissue inhibitor of metalloproteinase 1 (TIMP-1), has been implicated in abdominal aortic aneurysm formation. Since the clinical and pathological features of KD include inflammation and weakening of blood vessels, we analyzed acute- and convalescent-phase paired plasma or serum samples from 31 KD patients, 7 patients who did not completely meet the criteria for KD, and 26 non-KD controls (9 febrile and 17 afebrile patients) for pro-MMP-9 (92 kDa) enzyme activity by gelatin zymography and for active MMP-9 (83 kDa), pro-MMP-9, and TIMP-1 protein levels by enzyme-linked immunosorbent assay. Statistical analysis was performed by using Student t tests, linear regression, and the Wilcoxon rank-sum test. Markedly elevated pro-MMP-9 enzymatic activity, pro-MMP-9 protein levels, and TIMP-1 protein levels were found during the acute phase of illness in patients with clinically established KD and in patients who were suspected of having KD but did not meet all of the criteria. There was no significant difference in active MMP-9 levels. Furthermore, pro-MMP-9 and TIMP-1 protein levels were significantly elevated among KD patients, compared to those of febrile and afebrile non-KD controls. The significantly elevated pro-MMP-9 enzyme and protein levels during the acute phase of KD may reflect vascular remodeling or an inflammatory response to a microbial agent, suggesting a pathophysiological role for MMP-9 in coronary aneurysm formation.
机译:川崎病(KD)是一种病因不明的急性,自限性多系统血管炎,影响婴儿和幼儿。除非及时用大剂量静脉注射丙种球蛋白和阿司匹林治疗,否则患者经常会发展为冠状动脉瘤。以前,与金属蛋白酶1(TIMP-1)的组织抑制剂复合分泌的基质金属蛋白酶9(MMP-9)与腹主动脉瘤的形成有关。由于KD的临床和病理特征包括炎症和血管衰弱,因此我们分析了31例KD患者,7例不完全符合KD标准的患者和恢复期的配对血浆或血清样本。 KD对照(9名发热和17名发热患者)通过明胶酶谱法检测MMP-9的活性(92 kDa),并通过酶检测MMP-9的活性(83 kDa),MMP-9的活性和TIMP-1的蛋白水平联免疫吸附测定。使用Student t 检验,线性回归和Wilcoxon秩和检验进行统计分析。在患有疾病的急性期中,临床上确诊的KD患者和怀疑患有KD但未发现KD的患者,发现pro-MMP-9的酶活性,pro-MMP-9的蛋白水平和TIMP-1的蛋白水平明显升高。符合所有条件。活跃的MMP-9水平没有显着差异。此外,与发热和发热的非KD对照相比,KD患者中的pro-MMP-9和TIMP-1蛋白水平显着升高。在KD急性期,前MMP-9的原酶和蛋白质水平显着升高可能反映了血管重塑或对微生物制剂的炎症反应,提示MMP-9在冠状动脉瘤形成中的病理生理作用。

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