Cardiac matrix remodelling in congestive heart failure: the role of matrix metalloproteinases

Background: Congestive heart failure (CHF), the most frequent reason for hospital admission of elderly patients, is an important and rapidly increasing cause of morbidity and mortality worldwide. Its development is accompanied by left-ventricle (LV) dilatation and pump dysfunction. The extracellular space in the heart is now recognized as an essential element of myocardial structure and function, and a dynamic participant in remodelling. The matrix metalloproteinases (MMPs) are an endogenous enzyme system responsible for extracellular collagen degradation and remodelling. Objectives: To evaluate the potential role of several MMPs (MMP-1, MMP-3 and MMP-9) in CHF. Patients and methods: We recruited 30 consecutive patients with moderate to severe CHF who presented for heart-failure management, along with 15 age- and sex-matched control participants. Two-dimensional and M-mode echocardiographic studies were used to assess LV size and function and hence assess LV remodelling. MMP-1, -3 and -9 concentrations in serum were measured by ELISA at the time of admission and diagnosis. Results: Serum levels of all 3 metalloproteinases were higher in patients with CHF than in controls; those of MMP-3 were markedly increased in patients with severe CHF. Conclusions: The association found between LV performance and MMP levels suggests that MMPs are implicated in CHF, that serum concentrations of MMPs may serve as markers for CHF, and that MMPs are a potential novel therapeutic target.