Deferoxamine-activated hypoxia-inducible factor-1 restores cardioprotective effects of sevoflurane postconditioning in diabetic rats.

Abstract

AIM:

The cardioprotective effects of sevoflurane postconditioning (SpostC) are eliminated under diabetic conditions, and the underlying mechanism for this phenomenon remains unclear. Many studies have demonstrated that the hypoxia-inducible factor-1 (HIF-1) signalling pathway in the myocardium is impaired under diabetic conditions. This study was to investigate whether deferoxamine (DFO)-induced activation of HIF-1 signalling pathway can restore the cardioprotective effects of SpostC in diabetic rats.

METHODS:

A model of myocardial ischaemia/reperfusion (I/R) injury was induced via ligation of the left anterior descending artery. SpostC was conducted by administering 1.0 MAC sevoflurane. After inducing the I/R injury, the following parameters were measured: myocardial infarct size, cardiac function, myocardial ultrastructure, mitochondrial respiratory function, respiratory chain enzyme activity, rate of reactive oxygen species (ROS) generation, and protein expression of HIF-1α, vascular endothelial growth factor (VEGF), cleaved caspase-3, Bcl-2 and Bax.

RESULTS:

After DFO activated HIF-1 in the impaired myocardium of diabetic rats, SpostC significantly upregulated the protein expression of HIF-1α and its downstream mediator VEGF. This improved myocardial mitochondrial respiratory function and respiratory chain enzyme activity and reduced ROS generation as well as the protein expression of cleaved caspase-3 and Bax. As a result, myocardial infarct size decreased, and cardiac function and mitochondrial ultrastructure improved.

CONCLUSION:

This study demonstrates for the first time that abolishment of the cardioprotective effects of SpostC in diabetic rats is associated with impairment of the HIF-1 signalling pathway and that DFO can activate HIF-1 to restore these cardioprotective effects of SpostC in diabetic rats.

• Authors: P Xie, L Yang, A Talaiti, J J Wu, J Yu, T Yu, H Y Wang, B Huang, Q Wu, Y Maimaitili, J Wang, H P Ma, Y N Yang, H Zheng
• Journal: Acta physiologica (Oxford, England) (Acta Physiol (Oxf)) Vol. 221 Issue 2 Pg. 98-114 (Oct 2017) ISSN: 1748-1716 [Electronic] England
• PMID: 28316125 (Publication Type: Journal Article)
• Copyright: © 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Chemical References

• Anesthetics, Inhalation
• Hypoxia-Inducible Factor 1
• Hypoxia-Inducible Factor 1, alpha Subunit
• Methyl Ethers
• Siderophores
• Sevoflurane
• Deferoxamine

Topics

• Anesthetics, Inhalation (pharmacology)
• Animals
• Deferoxamine (pharmacology)
• Diabetes Mellitus, Experimental (metabolism)
• Gene Expression Regulation (drug effects)
• Hypoxia-Inducible Factor 1 (genetics, metabolism)
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Ischemic Postconditioning
• Male
• Methyl Ethers (pharmacology)
• Myocardial Infarction (metabolism)
• Myocardial Reperfusion Injury (drug therapy)
• Rats
• Rats, Sprague-Dawley
• Sevoflurane
• Siderophores (pharmacology)
• Signal Transduction
• Up-Regulation