© 2008 European Society of Cardiology
Relationships between plasma levels of matrix metalloproteinases and neurohormonal profile in patients with heart failure
Terrence Donnelly Heart Centre, Division of Cardiology, St. Michael's Hospital, University of Toronto Toronto, Ontario, Canada
Heart & Stroke/Richard Lewar Centre of Excellence, University of Toronto Canada
Department of Physiology, University of Toronto Canada
Division of Cardiology, Toronto General Hospital, University Health Network Toronto, Canada
Institute of Circulatory and Respiratory Health, Canadian Institutes of Health Research
Division of Cardiology, McMaster Health Science Centre Hamilton, Ontario, Canada
Department of Surgery, Medical University of South Carolina Charleston, SC, USA
* Corresponding authors. Liu is to be contacted at Heart & Stroke/Richard Lewar Centre of Excellence, NCSB 11-1266, Toronto General Hospital, 200 Elizabeth Street, Toronto, Ontario, Canada, M5G 2C4 Tel.: +1 416 340 3035; fax: +1 416 340 4753. McKelvie, McMaster University, Hamilton Health Sciences Centre, Hamilton, Ontario, Canada. Tel.: +1 905 572 7155; fax: +1 905 577 1480. E-mail addresses: mckelrob{at}hhsc.ca (R.S. McKelvie), peter.liu{at}utoronto.ca (P.P. Liu).
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Abstract |
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Background: Both neurohormonal derangements and alterations in the myocardial extracellular matrix are thought to contribute to adverse ventricular remodelling that results in worsening heart failure (HF). There is also emerging preclinical information to suggest that these signalling pathways mutually regulate in HF.
Aim: To assess the relationships between plasma levels of matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinase (TIMP), and neurohormonal profiles in chronic HF.
Methods and results: In this substudy of 184 HF patients enrolled in the Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) trial, plasma norepinephrine and epinephrine were measured with HPLC; atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), angiotensin II, aldosterone, and endothelin-1 were measured with immunoassays; MMP-2, MMP-9, and TIMP-1 were measured with 2-site sandwich ELISA assays. We used Spearman's rank correlation to examine the relationships between plasma MMP and neurohormone levels. Circulating ANP, BNP, and endothelin-1 levels were positively correlated with MMP-2 and TIMP-1 levels. Plasma level of aldosterone showed a weak positive correlation with MMP-9, but there was no significant correlation between angiotensin II, epinephrine or norepinephrine and MMP-2, MMP-9, or TIMP-1.
Conclusions: These findings suggest that specific neurohormones and extracellular matrix modulators may play a coordinated role in the pathogenesis of HF.
Key Words: Heart failure • Matrix metalloproteinase • Neurohormones
Received August 2, 2007; Revised November 9, 2007; Accepted December 5, 2007
1 Dr. Liu is the Scientific Director, Institute of Circulatory and Respiratory Health Canadian Institutes of Health Research; and the Heart & Stroke/Polo Chair Professor of Medicine and Physiology at the University Health Network, University of Toronto.
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