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European Heart Journal Advance Access originally published online on December 17, 2004
European Heart Journal 2005 26(5):481-488; doi:10.1093/eurheartj/ehi073
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© The European Society of Cardiology 2005. All rights reserved. For Permissions, please e-mail: journals.permissions{at}oupjournals.org

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

Cristina Banfi1,2,*, Viviana Cavalca2,3, Fabrizio Veglia2, Maura Brioschi1,2, Simona Barcella1, Luciana Mussoni1, Loredana Boccotti3, Elena Tremoli1,2, Paolo Biglioli2,3 and PierGiuseppe Agostoni2,3

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

Received 18 May 2004; revised 4 November 2004; accepted 15 November 2004; online publish-ahead-of-print 17 December 2004.

* Corresponding author. Tel: +39 0250318357; fax: +39 0250318250. E-mail address: cristina.banfi{at}unimi.it

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 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.

Key Words: Metalloproteinases • Heart failure • Catecholamines • Noradrenaline


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