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The Role of Macrophage Migration Inhibitory Factor in Remote Ischemic Postconditioning
- Source :
- Canadian Journal of Cardiology. 35:501-510
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Remote ischemic postconditioning (RIPostC) could reduce myocardial ischemia/reperfusion injury markedly. However, the mechanism of the protective signal transfer of RIPostC to the heart remains unclear. In this study, we hypothesize that macrophage migration inhibitory factor (MIF) plays an important role in the cardioprotection conferred by RIPostC.RIPostC was induced by 4 cycles of 5 min ischemia/5 min reperfusion on the lower limbs of rats immediately after myocardial reperfusion. The plasma level of MIF was compared between the RIPostC and reperfusion injury groups. (S,R)-3-(4-hydroxy -phenyl)-4,5-dihydro-5-isoxazoleacetic acid methyl ester (ISO-1) was used as a potent inhibitor of MIF. 2-methoxyestradiol (2ME2), an inhibitor of HIF-1α (hypoxia-inducible factor-1α),was used as a tool to inhibit the role of HIF-1α.We found that a significant elevation in the level of plasma MIF occurred when RIPostC was carried out; this elevation could be blocked by femoral occlusion. The cardiac MIF level decreased significantly after RIPostC stimulus compared with the ischemia/reperfusion (IR) group (P0.01). In addition, inhibition of MIF by ISO-1 could induce the loss of cardioprotection and aggravate the apoptosis of the heart in RIPostC. RIPostC confers protection against myocardial IR injury via the MIF-AMPK signaling pathway. Finally, inhibition of HIF-1α may result in the reduction of plasma MIF in RIPostC.MIF plays an important role in RIPostC through the humoral pathway in a HIF-1α-dependent manner, which could activate the cardiac AMP-activated protein kinase (AMPK) pathway to confer powerful cardioprotection.
- Subjects :
- Hypoxia-Inducible Factor 1
Ischemia
Apoptosis
Myocardial Reperfusion Injury
AMP-Activated Protein Kinases
030204 cardiovascular system & hematology
Pharmacology
03 medical and health sciences
0302 clinical medicine
medicine
Animals
030212 general & internal medicine
Rats, Wistar
Ischemic Postconditioning
Protein kinase A
Macrophage Migration-Inhibitory Factors
Cardioprotection
business.industry
Myocardium
AMPK
Isoxazoles
Hypoxia-Inducible Factor 1, alpha Subunit
medicine.disease
2-Methoxyestradiol
Macrophage migration inhibitory factor
Cardiology and Cardiovascular Medicine
business
Reperfusion injury
Subjects
Details
- ISSN :
- 0828282X
- Volume :
- 35
- Database :
- OpenAIRE
- Journal :
- Canadian Journal of Cardiology
- Accession number :
- edsair.doi.dedup.....fb265900fe4ab7bc6e94ad8ed94222b0