Matrix metalloproteinases and their inhibitors in malignant and autoreactive pericardial effusion

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.