Remote ischemic preconditioning confers late protection against myocardial ischemia–reperfusion injury in mice by upregulating interleukin-10

Remote ischemic preconditioning confers late protection against myocardial ischemia–reperfusion injury in mice by upregulating interleukin-10

Remote ischemic preconditioning (RIPC) induces a prolonged late phase of multi-organ protection against ischemia–reperfusion (IR) injury. In the present study, we tested the hypothesis that RIPC confers late protection against myocardial IR injury by upregulating expression of interleukin (IL)-10. M...

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Bibliographic Details
Published in:Basic research in cardiology 2012-07, Vol.107 (4), p.277-277, Article 277
Main Authors: Cai, Zheqing P., Parajuli, Nirmal, Zheng, Xiaoxu, Becker, Lewis
Format: Article
Language:eng
Subjects:
Animals
Blotting, Western
Cardiology
Immunoprecipitation
Interleukin-10 - biosynthesis
Ischemic Preconditioning, Myocardial - methods
Medicine
Medicine & Public Health
Mice
Mice, Inbred C57BL
Mice, Knockout
Myocardial Reperfusion Injury - metabolism
Myocardial Reperfusion Injury - prevention & control
Original Contribution
Up-Regulation
Online Access:Get full text
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Summary:Remote ischemic preconditioning (RIPC) induces a prolonged late phase of multi-organ protection against ischemia–reperfusion (IR) injury. In the present study, we tested the hypothesis that RIPC confers late protection against myocardial IR injury by upregulating expression of interleukin (IL)-10. Mice were exposed to lower limb RIPC or sham ischemia. After 24 h, mice with RIPC demonstrated decreased myocardial infarct size and improved cardiac contractility following 30-min ischemia and 120-min reperfusion (I-30/R-120). These effects of RIPC were completely blocked by anti-IL-10 receptor antibodies. In IL-10 knockout mice, RIPC cardioprotection was lost, but it was mimicked by exogenous IL-10. Administration of IL-10 to isolated perfused hearts increased phosphorylation of the protein kinase Akt and limited infarct size after I-30/R-120. In wild-type mice, RIPC increased plasma and cardiac IL-10 protein levels and caused activation of Akt and endothelial nitric oxide synthase in the heart at 24 h, which was also blocked by anti-IL-10 receptor antibodies. In the gastrocnemius muscle, RIPC resulted in immediate inactivation of the phosphatase PTEN and activation of Stat3, with increased IL-10 expression 24 h later. Myocyte-specific PTEN inactivation led to increased Stat3 phosphorylation and IL-10 protein expression in the gastrocnemius muscle. Taken together, these results suggest that RIPC induces late protection against myocardial IR injury by increasing expression of IL-10 in the remote muscle, followed by release of IL-10 into the circulation, and activation of protective signaling pathways in the heart. This study provides a scientific basis for the use of RIPC to confer systemic protection against IR injury.
ISSN:0300-8428
1435-1803