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Tumor necrosis factor-alpha and myocardial remodeling in progression of heart failure: a current perspective

William S Bradham1, Biykem Bozkurt, Himali Gunasinghe

  • 1Medical University of South Carolina, Charleston, SC 29425, USA.

Cardiovascular Research
|April 2, 2002
PubMed

Insights

Tumor necrosis factor alpha (TNF-alpha) contributes to heart failure by promoting left ventricular (LV) remodeling. This involves activating TNF receptors, leading to matrix metalloproteinases (MMPs) that degrade heart tissue.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Biochemistry

Background:

  • Congestive heart failure (CHF) progression involves myocardial remodeling, particularly in the left ventricle (LV).
  • Increased tumor necrosis factor alpha (TNF-alpha) release is linked to LV remodeling and dysfunction in CHF.
  • TNF-alpha exerts its effects via TNF receptors on cardiac cells, initiating cellular and molecular changes.

Purpose of the Study:

  • To explore the role of TNF-alpha and its receptors in LV myocardial remodeling during CHF.
  • To investigate the involvement of matrix metalloproteinases (MMPs) in TNF-alpha-mediated cardiac remodeling.
  • To identify potential therapeutic targets for mitigating CHF progression.

Main Methods:

  • Review of clinical and experimental studies on TNF-alpha, TNF receptors, and LV remodeling in CHF.
  • Analysis of in vitro studies demonstrating TNF receptor activation of proteolytic systems.
  • Examination of MMP upregulation in models of LV dysfunction.

Main Results:

  • TNF-alpha induction leads to LV dilation and pump dysfunction.
  • TNF receptor activation triggers cellular events contributing to LV remodeling, including myocyte changes and altered myocardial composition.
  • TNF receptor activation induces MMPs, a proteolytic system that degrades extracellular matrix components.

Conclusions:

  • TNF-alpha influences LV myocardial remodeling through the induction of specific MMPs.
  • Targeting TNF receptor activity and MMPs may offer future therapeutic strategies for CHF.
  • Further research is needed to elucidate the direct relationship between TNF receptor activity, MMPs, and LV remodeling in CHF.

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