Abstract 13918: Activation of Protective Intracellular Signaling Pathways in the Heart by Skeletal Muscle-Derived Cytokines During Remote Ischemic Preconditioning
Background: Although remote ischemic preconditioning (RIPC) has cardioprotective effects in ischemia/reperfusion injury, the mechanism of cardioprotection during RIPC is not fully understood. Hematopoietic or gp130 cytokines have been shown to have cardioprotective effects in ischemia/reperfusion injury. We hypothesized that skeletal muscle derived-cytokines induced by RIPC would activate cardiac intracellular signaling that has cardioprotective effects on ischemia/reperfusion injury.
Methods and Results: We measured plasma levels of cytokines before and after RIPC in healthy volunteers (n=10). RIPC was induced by three 5-minute episodes of right upper limb ischemia with an automated blood pressure cuff inflated to 200 mmHg and by 5 minutes of cuff deflation for reperfusion. We found that interleukin-6 (IL-6) and G-CSF were significantly increased 24 hours after RIPC (IL-6: from 0.23 ± 0.05 to 0.62 ± 0.06 pg/ml, p<0.05, G-CSF: from 15.9 ± 2.3 to 30.62 ± 4.2 pg/ml, p<0.05). Next, we examined the expression of cytokines in skeletal muscle after RIPC in mice (n=3). RIPC was induced by three cycles of 5 minutes of occlusion and 5 minutes of reperfusion of the right femoral artery. Real-time PCR revealed that multiple cytokines including G-CSF, IL-6 and IL-10 were increased 3 hours after RIPC (G-CSF; 2.3 fold, p<0.05, IL-6; 62.3 fold, p<0.05, IL-10; 18.4 fold, p<0.05). To investigate the effect of skeletal muscle-derived cytokines on the heart, we examined phosphorylation of intracellular signaling molecules such as STAT3 and AKT in the heart after RIPC. We found that STAT3 was transiently phosphorylated and AKT was gradually phosphorylated after RIPC, suggesting that circulating skeletal muscle-derived cytokines activate protective intercellular signaling in the heart.
Conclusion: These results suggest that expression of skeletal muscle-derived cytokines induced by RIPC may be a mechanism of cardioprotection during ischemia/reperfusion injury.
- © 2010 by American Heart Association, Inc.