Matrix Metalloproteinases 2 and 9 Are Differentially Expressed in Patients with Indeterminate and Cardiac Clinical Forms of Chagas Disease
Matrix Metalloproteinases 2 and 9 Are Differentially Expressed in Patients with Indeterminate and Cardiac Clinical Forms of Chagas Disease
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DOI：
10.1128/iai.00153-13
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发表时间：
2013-10-01
影响因子：
3.1
通讯作者：
Correa-Oliveira, Rodrigo
中科院分区：
文献类型：
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作者：
Gomes Fares, Rafaelle Christine;Silva Gomes, Juliana de Assis;Correa-Oliveira, Rodrigo
扩张型慢性心肌病（DCC）与心肌重塑和间质纤维化有关，导致细胞外基质（ECM）变化。在这项研究中，我们的特点是第一次血清基质金属蛋白酶2（MMP-2）和MMP-9的水平，以及他们的主要细胞来源的外周血单核细胞与不确定（IND）或心脏（CARD）的临床形式的查加斯病患者。我们的研究结果表明，血清MMP-9水平与南美锥虫病的严重程度有关。T淋巴细胞产生MMP的分析表明，CD 8（+）T细胞是MMP-2和MMP-9分子的主要单核白细胞来源。使用一个新的三维纤维化模型，我们观察到，锥虫病患者的血清诱导心脏球体细胞外基质成分的增加。此外，MMP-2和MMP-9在恰加斯病患者中与基质蛋白和炎性细胞因子表现出不同的相关性。我们的结果表明，MMP-2和MMP-9在恰加斯病发病机制中表现出不同的活性。虽然MMP-9似乎参与了恰加斯病的炎症和心脏重塑，但MMP-2与炎症分子无关。
Dilated chronic cardiomyopathy (DCC) from Chagas disease is associated with myocardial remodeling and interstitial fibrosis, resulting in extracellular matrix (ECM) changes. In this study, we characterized for the first time the serum matrix metalloproteinase 2 (MMP-2) and MMP-9 levels, as well as their main cell sources in peripheral blood mononuclear cells from patients presenting with the indeterminate (IND) or cardiac (CARD) clinical form of Chagas disease. Our results showed that serum levels of MMP-9 are associated with the severity of Chagas disease. The analysis of MMP production by T lymphocytes showed that CD8(+) T cells are the main mononuclear leukocyte source of both MMP-2 and MMP-9 molecules. Using a new 3-dimensional model of fibrosis, we observed that sera from patients with Chagas disease induced an increase in the extracellular matrix components in cardiac spheroids. Furthermore, MMP-2 and MMP-9 showed different correlations with matrix proteins and inflammatory cytokines in patients with Chagas disease. Our results suggest that MMP-2 and MMP-9 show distinct activities in Chagas disease pathogenesis. While MMP-9 seems to be involved in the inflammation and cardiac remodeling of Chagas disease, MMP-2 does not correlate with inflammatory molecules.