Lamparter Steffen, Schoppet Michael, Christ Michael, Pankuweit Sabine, Maisch Bernhard
Diakonie Krankenhaus Wehrda, Department of Internal Medicine, Marburg, Germany.
Am J Cardiol. 2005 May 1;95(9):1065-9. doi: 10.1016/j.amjcard.2004.12.059.
Matrix metalloproteinases (MMPs) are proteolytic enzymes essentially involved in tissue remodeling and tumor invasion, and their activity is counterbalanced by endogenous antagonists, the tissue inhibitors of matrix proteinases (TIMPs). Recent reports have suggested a potential role of MMPs in the evolution of pericardial effusion (PE). In this study, we determined the levels of MMP-2 and MMP-9 and their inhibitors TIMP-1 and TIMP-2 in 19 patients who had malignant PE that was confirmed by histology or cytology and 30 patients who had nonmalignant, autoreactive PE compared with pericardial fluid of 19 patients who had preserved left ventricular function and who underwent aortocoronary bypass surgery for control. Samples were assayed by zymography, immunoblotting, and quantitative enzyme-linked immunosorbent assay. We found significantly higher MMP-2 levels in malignant PE than in pericardial fluid (2,906 +/- 348 vs 1,493 +/- 114 ng/ml, p = 0.0005) or autoreactive PE (2,079 +/- 269 ng/ml, p = 0.01). No significant differences in MMP-9 levels were found between malignant PE and autoreactive PE (83 +/- 28.6 vs 106 +/- 30.4 ng/ml, p = 0.22), whereas MMP-9 was below the detection limit in pericardial fluid. No differences in TIMP-1 levels were found across the different study groups, whereas compared with pericardial fluid, TIMP-2 levels were significantly lower in autoreactive PE (113 +/- 18.9 vs 187 +/- 12.2 ng/ml, p = 0.002). In addition, there was a trend to lower TIMP-2 levels in malignant PE (137 +/- 27.1 ng/ml, p = 0.07). The present findings indicate that proteolytic enzymes and their inhibitors are involved in the pathogenesis of PE, with an expression pattern that depends on etiology. The involvement of MMP-2 in the pathogenesis of malignant PE may indicate a potential role of MMP inhibitors in the control of malignant PE.
基质金属蛋白酶（MMPs）是主要参与组织重塑和肿瘤侵袭的蛋白水解酶，其活性受到内源性拮抗剂——基质蛋白酶组织抑制剂（TIMPs）的制衡。最近的报道表明MMPs在心包积液（PE）的发展过程中可能发挥作用。在本研究中，我们测定了19例经组织学或细胞学确诊为恶性PE患者、30例非恶性自身反应性PE患者的心包积液中MMP-2和MMP-9及其抑制剂TIMP-1和TIMP-2的水平，并与19例左心室功能正常且接受主动脉冠状动脉搭桥手术的患者的心包积液作对照。通过酶谱分析、免疫印迹和定量酶联免疫吸附测定法对样本进行检测。我们发现，恶性PE患者心包积液中的MMP-2水平显著高于对照组心包积液（2,906±348 vs 1,493±114 ng/ml，p = 0.0005）或自身反应性PE患者的心包积液（2,079±269 ng/ml，p = 0.01）。恶性PE与自身反应性PE患者的心包积液中MMP-9水平无显著差异（83±28.6 vs 106±30.4 ng/ml，p = 0.22），而对照组心包积液中MMP-9低于检测限。不同研究组之间TIMP-1水平无差异，而与对照组心包积液相比，自身反应性PE患者的心包积液中TIMP-2水平显著降低（113±18.9 vs 187±12.2 ng/ml，p = 0.002）。此外，恶性PE患者的心包积液中TIMP-2水平也有降低趋势（137±27.1 ng/ml，p = 0.07）。目前的研究结果表明，蛋白水解酶及其抑制剂参与了PE的发病机制，其表达模式取决于病因。MMP-2参与恶性PE的发病机制可能表明MMP抑制剂在控制恶性PE方面具有潜在作用。
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