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.
Highlights
Reperfusin therapy is the gold standard in the treatment of acute ischemia and infarction, but restoration of blood flow to ischemic tissue results in the paradoxical phenomenon known as ischemia/reperfusion (I/R) injury
Myocardial I/R injury was significantly reduced by ischemic postconditioning (IPoC)
Plasma leakage of Lactate dehydrogenase (LDH) and creatine kinase MB (CK-MB) in the IPoC group was suppressed compared with that in the I/R group (P < 0.05). Both LDH and CK-MB activities was diminished at 24 h, with no obvious changes in LDH or CK-MB release in the sham group (Figures 1B and 1C)
Summary
Reperfusin therapy is the gold standard in the treatment of acute ischemia and infarction, but restoration of blood flow to ischemic tissue results in the paradoxical phenomenon known as ischemia/reperfusion (I/R) injury. I/R injury could be altered by endogenous protective strategies applied at different time points (Yellon and Hausenloy, 2007), and two endogenous protections were investigated most: ischemic preconditioning (IPC) and ischemic postconditioning (IPoC). IPC is defined as the cardioprotection conferred by multiple and brief episodes of occlusion/reperfusion (intermittent hypoperfusion) against the development of irreversible damage following a subsequent, more severe ischemic episode (Murry et al, 1986). IPoC denotes a condition in which a decrease in the infarct size results from brief periods of ischemia alternating with brief periods of reperfusion applied immediately during reperfusion following an ischemic insult
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