TNF-alpha and myocardial matrix metalloproteinases in heart failure: relationship to LV remodeling

1  Medical University of South Carolina, Charleston, South Carolina 29425; and 2  St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada M5B 1W8 The cytokine tumor necrosis factor (TNF)- has been causally linked to left ventricular (LV) remodeling, but the molecular basis for t...

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Published in:American journal of physiology. Heart and circulatory physiology 2002-04, Vol.282 (4), p.H1288-H1295
Main Authors: Bradham, William S, Moe, Gordon, Wendt, Katherine A, Scott, Amelia A, Konig, Andrea, Romanova, Marina, Naik, George, Spinale, Francis G
Format: Article
Language:English
Subjects:
Animals
Antibodies - pharmacology
Disease Models, Animal
Dogs
Heart Failure - physiopathology
Heart Rate - physiology
Isoenzymes - metabolism
Matrix Metalloproteinase 2 - metabolism
Matrix Metalloproteinase 8 - metabolism
Matrix Metalloproteinases - metabolism
Myocardium - enzymology
Tissue Inhibitor of Metalloproteinase-1 - metabolism
Tissue Inhibitor of Metalloproteinase-4
Tissue Inhibitor of Metalloproteinases - metabolism
Tumor Necrosis Factor-alpha - immunology
Tumor Necrosis Factor-alpha - physiology
Ventricular Function, Left - physiology
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Summary:1  Medical University of South Carolina, Charleston, South Carolina 29425; and 2  St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada M5B 1W8 The cytokine tumor necrosis factor (TNF)- has been causally linked to left ventricular (LV) remodeling, but the molecular basis for this effect is unknown. Matrix metalloproteinases (MMPs) have been implicated in cardiac remodeling and can be regulated by TNF- . This study tested the central hypothesis that administration of a TNF- blocking protein would prevent the induction of MMPs and alter the course of myocardial remodeling in developing LV failure. Adult dogs were randomly assigned to the following groups: 1 ) chronic pacing (250 beats/min, 28 days, n  = 12), 2 ) chronic pacing with concomitant administration of a TNF- blocking protein (TNF block) using a soluble p75 TNF receptor fusion protein (TNFR:Fc; administered at 0.5 mg/kg twice a week subcutaneously, n  = 7), and 3 ) normal controls ( n  = 10). LV end-diastolic volume increased from control with chronic pacing (83 ± 12 vs. 118 ± 10 ml, P  <   0.05) and was reduced with TNF block (97 ± 9 ml, P  
ISSN:0363-6135
1522-1539
DOI:10.1152/ajpheart.00526.2001