Increased activities of cardiac matrix metalloproteinases matrix metalloproteinase (MMP)-2 and MMP-9 are associated with mortality during the acute phase of experimental Trypanosoma cruzi infection
Increased activities of cardiac matrix metalloproteinases matrix metalloproteinase (MMP)-2 and MMP-9 are associated with mortality during the acute phase of experimental Trypanosoma cruzi infection
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DOI：
10.1086/587487
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发表时间：
2008-05-15
影响因子：
6.4
通讯作者：
Silva, Joao Santana
中科院分区：
文献类型：
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作者：
Salazar Gutierrez, Fredy Roberto;Lalu, Manoj Mathew;Silva, Joao Santana
在克氏锥虫感染的急性期，心脏中发生的强烈炎症反应受到白细胞和心肌细胞产生的细胞因子和趋化因子的调节。基质金属蛋白酶（MMPs）最近出现作为心血管炎症的调节剂。在本研究中，我们研究了MMP-2和MMP-9在T.采用免疫组化、明胶酶谱、酶联免疫吸附试验和实时荧光聚合酶链反应等方法对克氏锥虫心肌组织进行分析。Cruzi感染的C57 BL/6小鼠。感染后第14天观察到MMP-2和MMP-9的转录水平、免疫反应性和酶活性增加。与对照组相比，用MMP抑制剂治疗的小鼠显示出显著降低的心脏炎症，寄生虫血症的峰值延迟，并且存活率提高。在治疗组中还观察到心脏肿瘤坏死因子-α、干扰素-γ、血清亚硝酸盐和血清硝酸盐水平降低。这些结果表明MMPs在T.克鲁兹引起的急性心肌炎
The strong inflammatory reaction that occurs in the heart during the acute phase of Trypanosoma cruzi infection is modulated by cytokines and chemokines produced by leukocytes and cardiomyocytes. Matrix metalloproteinases (MMPs) have recently emerged as modulators of cardiovascular inflammation. In the present study we investigated the role of MMP-2 and MMP-9 in T. cruzi-induced myocarditis, by use of immunohistochemical analysis, gelatin zymography, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction to analyze the cardiac tissues of T. cruzi-infected C57BL/6 mice. Increased transcripts levels, immunoreactivity, and enzymatic activity for MMP-2 and MMP-9 were observed by day 14 after infection. Mice treated with an MMP inhibitor showed significantly decreased heart inflammation, delayed peak in parasitemia, and improved survival rates, compared with the control group. Reduced levels of cardiac tumor necrosis factor-alpha, interferon-gamma, serum nitrite, and serum nitrate were also observed in the treated group. These results suggest an important role for MMPs in the induction of T. cruzi-induced acute myocarditis.