Exp Mol Med.  2011 Aug;43(8):437-445. 10.3858/emm.2011.43.8.049.

Ischemic postconditioning protects cardiomyocytes against ischemia/reperfusion injury by inducing MIP2

• Zhu HL
• Wei X
• Qu SL
• Zhang C
• Zuo XX
• Feng YS
• Luo Q
• Chen GW
• Liu MD
• Jiang L
• Xiao XZ
• Wang KK

• KMID: 1022118
• DOI: http://doi.org/10.3858/emm.2011.43.8.049

Abstract

Cardiomyocytes can resist ischemia/reperfusion (I/R) injury through ischemic postconditioning (IPoC) which is repetitive ischemia induced during the onset of reperfusion. Myocardial ischemic preconditioning up-regulated protein 2 (MIP2) is a member of the WD-40 family proteins, we previously showed that MIP2 was up-regulated during ischemic preconditioning (IPC). As IPC and IPoC engaged similar molecular mechanisms in cardioprotection, this study aimed to elucidate whether MIP2 was up-regulated during IPoC and contributed to IPoC-mediated protection against I/R injury. The experiment was conducted on two models, an in vivo open chest rat coronary artery occlusion model and an in vitro model with H9c2 myogenic cells. In both models, 3 groups were constituted and randomly designated as the sham, I/R and IPoC/hypoxia postconditioning (HPoC) groups. In the IPoC group, after 45 min of ischemia, hearts were allowed three cycles of reperfusion/ischemia phases (each of 30 s duration) followed by reperfusion. In the HPoC group, after 6 h of hypoxia, H9c2 cells were subjected to three cycles of 10 minute reoxygenation and 10 minute hypoxia followed by reoxygenation. IPoC significantly reduced the infarct size, plasma level of Lactate dehydrogenase and creatine kinase MB in rats. 12 h after the reperfusion, MIP2 mRNA levels in the IPoC group were 10 folds that of the sham group and 1.4 folds that of the I/R group. Increased expression of MIP2 mRNA and attenuation of apoptosis were similarly observed in the HPoC group in the in vitro model. These effects were blunted by transfection with MIP2 siRNA in the H9c2 cells. This study demonstrated that IPoC induced protection was associated with increased expression of MIP2. Both MIP2 overexpression and MIP2 suppression can influence the IPoC induced protection.

Keyword

ischemic preconditioning, myocardial; myocardial ischemia; myocardial reperfusion; reperfusion injury

MeSH Terms

Animals
Blotting, Western
Cell Hypoxia/genetics/physiology
Cell Line
Cell Survival/genetics/physiology
Flow Cytometry
Ischemic Preconditioning, Myocardial/*methods
Male
Myocytes, Cardiac/*metabolism/*pathology
Rats
Rats, Sprague-Dawley
Real-Time Polymerase Chain Reaction
Reperfusion Injury/*metabolism/*prevention & control