The SAFE pathway for cardioprotection: is this a promising target?

Nkanyiso Hadebe; Martin Cour; Sandrine Lecour

doi:10.1007/s00395-018-0670-5

The SAFE pathway for cardioprotection: is this a promising target?

Basic Res Cardiol. 2018 Jan 15;113(2):9. doi: 10.1007/s00395-018-0670-5.

Authors

Nkanyiso Hadebe^{1

2

3}, Martin Cour^{1

2}, Sandrine Lecour^{4

5}

Affiliations

¹ Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town, 7925, South Africa.
² Lionel Opie Preclinical Imaging Core Facility, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
³ Department of Anaesthesia, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
⁴ Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town, 7925, South Africa. Sandrine.lecour@uct.ac.za.
⁵ Lionel Opie Preclinical Imaging Core Facility, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. Sandrine.lecour@uct.ac.za.

PMID: 29335904
DOI: 10.1007/s00395-018-0670-5

Abstract

The survivor activating factor enhancement (SAFE) pathway was discovered as an alternative intrinsic pro-survival signaling pathway to the reperfusion injury salvage kinase pathway for cardioprotection against ischemia-reperfusion injury. The delineation of this pathway, made of key components such as cytokines of the immune system and transcription factors, has brought major advancements in our understanding on how the heart is able to protect itself against ischemia-reperfusion injury. In this viewpoint, we describe the major steps leading to the discovery of the SAFE pathway in small animal models to date and we discuss its translation to large animals and humans.

Keywords: Cardioprotection; Immune system; Ischemia–reperfusion injury; Prosurvival signaling pathways; SAFE pathway.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Cardiovascular Agents / therapeutic use
Drug Design
Humans
Molecular Targeted Therapy
Myocardial Infarction / metabolism*
Myocardial Infarction / pathology
Myocardial Infarction / physiopathology
Myocardial Infarction / prevention & control
Myocardial Reperfusion Injury / metabolism*
Myocardial Reperfusion Injury / pathology
Myocardial Reperfusion Injury / physiopathology
Myocardial Reperfusion Injury / prevention & control
Myocytes, Cardiac / drug effects
Myocytes, Cardiac / metabolism*
Myocytes, Cardiac / pathology
Receptors, Tumor Necrosis Factor, Type II / metabolism
STAT3 Transcription Factor / metabolism
Signal Transduction / drug effects
Tumor Necrosis Factor-alpha / antagonists & inhibitors
Tumor Necrosis Factor-alpha / metabolism*

Substances

Cardiovascular Agents
Receptors, Tumor Necrosis Factor, Type II
STAT3 Transcription Factor
Tumor Necrosis Factor-alpha