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European Heart Journal Advance Access published online on December 17, 2004
European Heart Journal, doi:10.1093/eurheartj/ehi073
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European Heart Journal © The European Society of Cardiology 2004; all rights reserved

Preclinical research

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

Cristina Banfi 1*, Viviana Cavalca 2, Fabrizio Veglia 3, Maura Brioschi 1, Simona Barcella 4, Luciana Mussoni 4, Loredana Boccotti 5, Elena Tremoli 1, Paolo Biglioli 2, and PierGiuseppe Agostoni 2

1 Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy; Centro Cardiologico Monzino, IRCCS, Milan, Italy
2 Centro Cardiologico Monzino, IRCCS, Milan, Italy; Institute of Cardiology, University of Milan, Milan, Italy
3 Centro Cardiologico Monzino, IRCCS, Milan, Italy
4 Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy
5 Institute of Cardiology, University of Milan, Milan, Italy

* To whom correspondence should be addressed.
Cristina Banfi, E-mail: cristina.banfi{at}unimi.it


  Abstract

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. 214ng/mL, P = 0.006; MMP-9 16.3 vs. 8.7ng/mL, P < 0.0001). Similarly, noradrenaline, but not adrenaline, was significantly higher in patients (noradrenaline 645 vs. 157pg/mL, P < 0.0001; adrenaline 86.0 vs. 72.6pg/mL, P = 0.68). No difference in any parameter was observed between patient groups. The intra-group correlation between MMP-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.

Keywords: Metalloproteinases; Heart failure; Catecholamines; Noradrenaline.
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