Neurohormonal activation is associated with increased levels of plasma matrix metalloproteinase-2 in human heart failure

Aims: Development of heart failure depends on systemic and molecular abnormalities among which are the activation of neurohormonal systems and the increase of matrix metalloproteinases (MMPs). This study assessed the relationship between catecholamines and active MMPs in vivo in patients with severe congestive heart failure (CHF) and in vitro in human cardiac fibroblasts. Methods and results: Forty patients with CHF due to dilated cardiomyopathy, either idiopathic (n = 20) or secondary to ischaemic heart disease (n = 20), were compared with 20 healthy subjects. Plasma MMP-2 and MMP-9 activity, but not TIMP-2, were significantly higher in patients than in controls (median MMP-2, 270 vs. 214 ng/mL, P = 0.006; MMP-9 16.3 vs. 8.7 ng/mL, P < 0.0001). Similarly, noradrenaline, but not adrenaline, was significantly higher in patients (noradrenaline 645 vs. 157 pg/mL, P < 0.0001; adrenaline 86.0 vs. 72.6 pg/mL, P = 0.68). No difference in any parameter was observed between patient groups. The intra-group correlation between MPP-2 and noradrenaline was significant (r = 0.33, P = 0.01); indeed, noradrenaline appear to be a predictor of MMP-2. Moreover, this catecholamine increased MMP-2 in human cardiac fibroblasts. Conclusions: The positive correlation between noradrenaline and MMP-2 in severe CHF patients, together with the in vitro induction of MMP-2 by this catecholamine, suggests a potential biochemical link between noradrenaline and MMP-2.