© 2002 by European Society of Cardiology
Copyright © 2002, European Society of Cardiology
Tumor necrosis factor-alpha and myocardial remodeling in progression of heart failure: a current perspective
aMedical University of South Carolina, Charleston, SC, USA
bWinters Center for Heart Failure Research, Section of Cardiology, Houston VAMC and Baylor College of Medicine, Houston, TX, USA
* Corresponding author. Cardiothoracic Surgery, Room 625, Strom Thurmond Research Building, 770 MUSC Complex, Medical University of South Carolina, 114 Doughty Street, Charleston, SC 29425, USA. Tel.: +1-843-876-5184; fax: +1-843-876-5187
A milestone in the progression of congestive heart failure (CHF) is myocardial remodeling. Left ventricular (LV) remodeling during the progression of CHF is accompanied by changes in the structure of the myocardial extracellular matrix. Recent clinical and experimental studies have noted that increased release of tumor necrosis factor alpha (TNF-
) can contribute to LV myocardial remodeling. Experimental studies have noted that the induction of TNF- can result in LV dilation and proceed to LV pump dysfunction. The biological effects of TNF- are mediated through TNF receptors that are present on all nucleated cells in the heart. TNF receptor activation can induce a number of cellular and molecular events which contribute to LV remodeling in CHF, and include changes in myocyte size and viability and alterations in myocardial structure/composition. In vitro studies have demonstrated that TNF receptor activation can cause the induction of a proteolytic system. This proteolytic system, the matrix metalloproteinases (MMPs), is upregulated in models of LV dysfunction and possesses the capacity to degrade a wide variety of extracellular matrix components. Therefore, one pathway by which TNF- can influence LV myocardial remodeling is through the induction of a specific portfolio of MMP species. Future basic and clinical studies which directly alter TNF receptor activity and measure myocardial MMP species and the relation to LV remodeling will provide new insight into this disease process and future therapeutic modalities.
KEYWORDS AP-1, Activating protein 1; CHF, Congestive heart failure; ECM, Extracellular matrix; LV, Left ventricle; LVEF, Left ventricular ejection fraction; MMP, Matrix metalloproteinase; MRI, Magnetic resonance imaging; NF-
B, Nuclear factor kappa B; NYHA, New York Heart Association; TNF-, Tumor necrosis factor alpha; TNFR1, Tumor necrosis factor alpha receptor type 1; TNFR2, Tumor necrosis factor alpha receptor type 2
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