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Activation of the protective Survivor Activating Factor Enhancement (SAFE) pathway against reperfusion injury: Does

Sandrine Lecour1

  • 1Cardioprotection Group, Hatter Cardiovascular Research Institute, Department of Medicine, Chris Barnard Building, Faculty of Health Sciences, University of Cape Town, 7925 Observatory, South Africa.

Journal of Molecular and Cellular Cardiology
|April 7, 2009
PubMed

Insights

Tumor necrosis factor alpha (TNFα) paradoxically activates a novel cardiac protective pathway, the Survivor Activating Factor Enhancement (SAFE) pathway, reducing lethal reperfusion injury. This SAFE pathway, involving STAT-3, offers a new therapeutic target for acute myocardial infarction.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Cellular Signaling

Background:

  • Lethal reperfusion injury is a significant complication of acute myocardial infarction treatment.
  • The heart possesses intrinsic mechanisms to protect against reperfusion-induced cell death.
  • Tumor necrosis factor alpha (TNFα) is typically associated with myocardial dysfunction.

Purpose of the Study:

  • To review evidence for a novel protective pathway initiated by TNFα against reperfusion injury.
  • To introduce the Survivor Activating Factor Enhancement (SAFE) pathway.
  • To explore the SAFE pathway's interaction with the Reperfusion Injury Salvage Kinase (RISK) pathway and its therapeutic potential.

Main Methods:

  • Review of existing scientific literature on TNFα, reperfusion injury, and cardiac signaling pathways.
  • Analysis of evidence supporting the role of signal transducer and activator of transcription 3 (STAT-3) in cardioprotection.
  • Comparison of the SAFE pathway with the established RISK pathway (involving Akt and Erk 1/2).

Main Results:

  • TNFα can paradoxically activate a protective signaling cascade, the SAFE pathway.
  • The SAFE pathway requires STAT-3 activation and limits cardiomyocyte death during reperfusion.
  • The SAFE pathway operates independently of the RISK pathway.

Conclusions:

  • The SAFE pathway represents a novel intrinsic cardiac protection mechanism against lethal reperfusion injury.
  • Understanding the SAFE pathway's interplay with the RISK pathway is crucial for therapeutic development.
  • Targeting the SAFE pathway holds potential for protecting hearts from reperfusion damage in clinical settings.

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