Related Experiment Video

Updated: Nov 26, 2025

Isolation of Functional Cardiac Immune Cells
07:26

Isolation of Functional Cardiac Immune Cells

Published on: December 5, 2011

15.3K

TNF-α signaling: TACE inhibition to put out the burning heart

Gesine M Dittrich1, Joerg Heineke1

  • 1Department of Cardiovascular Physiology, European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Plos Biology
|December 9, 2020
PubMed

Insights

Targeting transmembrane TNF-α (tmTNF-α), a precursor form of tumor necrosis factor alpha, may offer a new therapeutic strategy for heart failure. This approach prevents tmTNF-α cleavage, potentially overcoming limitations of previous cytokine inhibition trials.

Area of Science:

  • Cardiovascular Research
  • Immunology
  • Molecular Medicine

Background:

  • Cytokines, such as tumor necrosis factor alpha (TNF-α), were long considered therapeutic targets for heart failure.
  • Previous clinical trials inhibiting TNF-α and other cytokines showed limited efficacy or adverse effects.

Purpose of the Study:

  • To investigate the role of transmembrane TNF-α (tmTNF-α) in pressure overload-induced cardiac remodeling.
  • To explore novel therapeutic strategies for heart failure by targeting TNF-α converting enzyme (TACE).

Main Methods:

  • Analysis of cardiac remodeling and function under pressure overload conditions.
  • Investigation of the effects of inhibiting tmTNF-α cleavage via TACE inhibition.

Main Results:

  • Transmembrane TNF-α (tmTNF-α) exhibits cardioprotective effects during cardiac remodeling.
  • Preventing tmTNF-α cleavage may be a more effective strategy than broad TNF-α inhibition.

Conclusions:

  • The membrane-bound precursor form of TNF-α (tmTNF-α) plays a protective role in heart failure.
  • Targeting TACE to prevent tmTNF-α cleavage represents a promising therapeutic avenue for heart failure treatment.

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