Imbalance of matrix metalloproteinases/tissue inhibitor of metalloproteinase-1 and loss of fibronectin expression in patients with congestive heart failure.

摘要

OBJECTIVE: Previous studies have demonstrated that an imbalance of matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinase-1 (TIMP-1) and a loss of fibronectin are associated with postmyocardial infarction remodeling in rats. The present study was designed to examine this issue in patients with congestive heart failure (CHF). METHODS: We measured plasma levels and the cardiac protein expression of MMPs/TIMP-1 and fibronectin in 39 patients with CHF and 38 controls. RESULTS: Plasma levels of MMP-2, MMP-3, and MMP-9 tended to be higher in patients with CHF (NYHA II: 276 +/- 18, 613 +/- 118, and 245 +/- 43 microg/l, respectively; NYHA III: 302 +/- 20, 850 +/- 132, and 310 +/- 39 microg/l, respectively; NYHA IV: 367 +/- 15, 998 +/- 99, and 392 +/- 27 microg/l, respectively) than in controls (213 +/- 23, 485 +/- 102, and 158 +/- 31 microg/l, respectively), while the plasma TIMP-1 level tended to be lower in patients with CHF (NYHA II: 126 +/- 12 microg/l, NYHA III: 83 +/- 11 microg/l, and NYHA IV: 61 +/- 12 microg/l) than in controls (208 +/- 15 microg/l). Interestingly, the changes in protein expression of MMPs/TIMP-1 were consistent with their plasma concentration. Furthermore, the fibronectin level in the patients with CHF was significantly lower than in the controls. Conclusions: These data suggest that human CHF is associated with an imbalance of MMPs/TIMP-1 and a concurrent loss of fibronectin.