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Myocardial Remodeling in Viral Heart Disease: Possible Interactions Between Inflammatory Mediators and MMP-TIMP System

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Abstract

Matrix metalloproteinases (MMP), a family of proteases, are involved in the degradation of extracellular matrix proteins and hence in the determination of interstitial architecture. In the heart, MMPs have been found to play a significant role in the development of myocardial remodeling and congestive heart failure. Tissue inhibitors of matrix metalloproteinases (TIMPs) represent a family of proteins which are known to regulate the expression and activity of MMPs. TIMPs are endogenous physiological inhibitors of MMPs and their concomitant downregulation in heart failure suggests the existence of a critical balance between MMPs and TIMPs in the normal maintenance of myocardial interstitial homeostasis. In addition, cytokines regulate expression of both MMPs and TIMPs besides eliciting a direct effect on myocardial cell function. Therefore, myocardial inflammation may also contribute to the development of cardiac remodeling along with other stimuli like mechanical stress and humoral factors. Viral myocarditis, a predisposing factor for dilated cardiomyopathy, is a condition in which extent of intramyocardial inflammation is thought to determine the progression of disease. Inflammatory events in the heart following viral infection are speculated to be responsible for the transition of myocarditis to dilated cardiomyopathy. In viral myocarditis and other inflammatory heart diseases, the inflammatory cells and their battery of cytokines may also alter the myocardial MMP-TIMP system and eventually lead to dilation of the heart and ventricular dysfunction. The objective of this review is to present an overall picture of the inflammatory phase in viral myocarditis and discuss the possible interactions between inflammation and myocardial MMP profiles which may lead to the evolution of dilated cardiomyopathy.

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  1. Department of Cardiology, University Hospital Benjamin Franklin, Free University Berlin, Hindenburgdamm 30, D-12200, Berlin, Germany

    Matthias Pauschinger, Kumaran Chandrasekharan & Heinz-Peter Schultheiss

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  1. Matthias Pauschinger
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  2. Kumaran Chandrasekharan
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  3. Heinz-Peter Schultheiss
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Pauschinger, M., Chandrasekharan, K. & Schultheiss, HP. Myocardial Remodeling in Viral Heart Disease: Possible Interactions Between Inflammatory Mediators and MMP-TIMP System. Heart Fail Rev 9, 21–31 (2004). https://doi.org/10.1023/B:HREV.0000011391.81676.3c

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