Abstract
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 µg/l, respectively; NYHA III: 302 ± 20, 850 ± 132, and 310 ± 39 µg/l, respectively; NYHA IV: 367 ± 15, 998 ± 99, and 392 ± 27 µg/l, respectively) than in controls (213 ± 23, 485 ± 102, and 158 ± 31 µg/l, respectively), while the plasma TIMP-1 level tended to be lower in patients with CHF (NYHA II: 126 ± 12 µg/l, NYHA III: 83 ± 11 µg/l, and NYHA IV: 61 ± 12 µg/l) than in controls (208 ± 15 µg/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.