Centro de Pesquisas René Rachou-FIOCRUZ, Belo Horizonte/MG, Brazil.
Infect Immun. 2013 Oct;81(10):3600-8. doi: 10.1128/IAI.00153-13. Epub 2013 Jul 15.
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.
扩张型慢性克氏锥虫病（DCC）与心肌重构和间质纤维化有关，导致细胞外基质（ECM）变化。在这项研究中，我们首次描述了来自不定型（IND）或心脏型（CARD）克氏锥虫病患者外周血单个核细胞中血清基质金属蛋白酶 2（MMP-2）和 MMP-9 水平及其主要细胞来源。我们的结果表明 MMP-9 血清水平与克氏锥虫病的严重程度相关。对 T 淋巴细胞 MMP 产生的分析表明，CD8(+)T 细胞是 MMP-2 和 MMP-9 分子的主要单核白细胞来源。使用新的纤维化 3D 模型，我们观察到克氏锥虫病患者的血清诱导心脏球体中细胞外基质成分增加。此外，在克氏锥虫病患者中，MMP-2 和 MMP-9 与基质蛋白和炎症细胞因子显示出不同的相关性。我们的结果表明 MMP-2 和 MMP-9 在克氏锥虫病发病机制中表现出不同的活性。虽然 MMP-9 似乎参与了克氏锥虫病的炎症和心肌重构，但 MMP-2 与炎症分子不相关。
