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When are pro-inflammatory cytokines SAFE in heart failure?
Sandrine Lecour1, Richard W James
1Hatter Cardiovascular Research Institute, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. sandrine.lecour@uct.ac.za
European Heart Journal
|February 10, 2011
Summary
Pro-inflammatory cytokines, linked to heart failure, may paradoxically activate a protective pathway called SAFE. This survival activating factor enhancement pathway, involving STAT3, offers new therapeutic targets for heart failure treatment.
Area of Science:
- Cardiovascular Science
- Immunology
- Molecular Biology
Background:
- The cytokine hypothesis posits that excessive pro-inflammatory cytokines (TNF, IL6) drive heart failure pathogenesis.
- This hypothesis, validated in animal models, has shown limited success in human clinical translation.
- Emerging data reveal pro-inflammatory cytokines can activate pro-survival pathways under specific conditions.
Purpose of the Study:
- To review the role of the novel SAFE pathway in heart failure.
- To explore the potential of targeting the SAFE pathway for heart failure prevention and treatment.
Main Methods:
- Review of recent experimental data on cytokine signaling in heart failure.
- Analysis of the SAFE pathway involving signal transducer and activator of transcription 3 (STAT3).
Main Results:
- Pro-inflammatory cytokines can activate the SAFE pathway, a pro-survival signaling cascade.
- The SAFE pathway involves the transcription factor STAT3, offering a counter-regulatory mechanism.
Conclusions:
- The SAFE pathway represents a potential therapeutic target for heart failure.
- Targeting the SAFE pathway could offer novel preventive and therapeutic strategies for heart failure.
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