Upregulation of extracellular matrix metalloproteinase inducer (EMMPRIN) and gelatinases in human atherosclerosis infected with Chlamydia pneumoniae:: The potential role of Chlamydia-pneumoniae infection in the progression of atherosclerosis
Upregulation of extracellular matrix metalloproteinase inducer (EMMPRIN) and gelatinases in human atherosclerosis infected with Chlamydia pneumoniae:: The potential role of Chlamydia-pneumoniae infection in the progression of atherosclerosis
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DOI：
10.1038/emm.2002.56
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发表时间：
2002-12-31
影响因子：
12.8
通讯作者：
Kim, HS
中科院分区：
文献类型：
--
作者：
Choi, EY;Kim, D;Kim, HS
肺炎衣原体感染被认为是动脉粥样硬化的重要病因，尤其是冠状动脉疾病（CAD），体外发现与基质金属蛋白酶（MMP）的诱导有关。诱导和激活 MMP 的细胞外基质金属蛋白酶诱导剂 (EMMPRIN)/膜 I 型基质金属蛋白酶 (MT1-MMP) 系统被认为具有功能，并且在衰竭心肌中上调。然而，粥样斑块内肺炎衣原体对 MMP 的上游调节仍不清楚。我们评估了 CAD 患者 (n = 391) 和对照 (n = 97) 肺炎衣原体感染的血清流行病学研究，并通过使用肺炎衣原体免疫化学、EMMPRIN/1-MMP、MMP-2 和 MMP-9 对从肺炎衣原体血清阳性患者 (n = 20) 获得的动脉粥样硬化血管组织进行了组织病理学和体外分析。两种抗C的血清阳性率。冠心病组肺炎链球菌IgG和IgA为56.7%，对照组为43.3%（P=0.033）。与具有传统危险因素的 CAD 患者亚组相比，不具有传统冠心病危险因素的 CAD 患者亚组的血清阳性率有所增加。 EMMPRIN、MT1-MMP、MMP-2 和 MMP-9 的免疫反应性在动脉粥样斑块本身中增加，主要是在对肺炎衣原体的免疫反应性巨噬细胞/单核细胞中。此外，Western印迹分析表明，与对照组织相比，在感染肺炎衣原体的动脉粥样硬化组织中更显着地检测到EMMPRIN和MMP-2。酶谱分析显示，与对照组织相比，感染肺炎衣原体的动脉粥样硬化组织中 MMP-2 和 MMP-9 的活性增加更多。本研究表明，动脉粥样硬化斑块内的肺炎衣原体可以诱导 MMP 的上游调节。这些发现有助于了解肺炎衣原体在动脉粥样硬化进展中的潜在作用。
Chlamydia pneumoniae infection implicated as an important etiologic factor of atherosclerosis, especially in coronary artery disease (CAD), was found in vitro to be associated with the induction of matrix metalloproteinases (MMPs). An extracellular matrix metalloproteinase inducer (EMMPRIN)/ membrane-type I matrix metal loproteinase (MT1-MMP) system which induces and activates MMPs, is suggested to be functional and were upregulated in the failing myocardium. However, the upstream regulation of MMPs by C. pneumoniae within atheroma itself remains unclear. We evaluated the seroepidemiologic study of C. pneumoniae infection in CAD patients (n = 391) and controls (n = 97) and performed histopathological and in vitro analysis in atherosclerotic vascular tissues obtained from patients with seropositive to C. pneumoniae (n = 20), by using immunochemistry for C. pneumoniae, EMMPRIN/1-MMP, MMP-2, and MMP-9. The seropositive rates of both anti-C. pneumoniae IgG and IgA were 56.7% in CAD group and 43.3% in control group (P=0.033). Seropositive rate was increased in subgroups of CAD patients without conventional coronary risk factors compared to those with conventional risk factors. Immunoreactivities of EMMPRIN, MT1-MMP, MMP-2, and MMP-9 were increased in the atheromatous plaque itself, predominantly in immunoreactive macrophages/mononuclear cells to C. pneumoniae. Furthermore, Western blot analysis showed that EMMPRIN and MMP-2 were detected more prominently in atherosclerotic tissues infected with C. pneumoniae compared to control tissues. Zymographic analysis revealed that activities of MMP-2 and MMP-9 were more increased in atherosclerotic tissues infected with C. pneumoniae compared to control tissues. The present study demonstrated upstream regulation of MMPs can be induced by C. pneumoniae within atheromatous plaque itself. These findings help to understand the potential role of C. pneumoniae in the progression of atherosclerosis.