Carbamylated Erythropoietin Protects the Myocardium From Acute Ischemia/Reperfusion Injury Through a PI3K/AKT-Dependent Mechanism
Background: Erythropoietin (EPO) and carbamylated erythropoietin (CEPO) can protect tissue from injury; however, CEPO has its protective effect in the absence of erythropoietic stimulation. The mechanism whereby CEPO protects heart from acute ischemia/reperfusion (I/R) injury remains unknown. Methods: BALB/c mice were subjected to myocardial ischemia for 45 min followed by reperfusion for 4 h, and they received a single dose of CEPO intraperitoneal at the onset of reperfusion. Myocardial infarct size and cardiac function were assessed. The association of erythropoietin receptor with β common receptor (βcR) was examined. The level of Akt phosphorylation in the myocardium was assayed as well as a series of downstream target genes of PI3K/Akt,including p-GATA-4, GATA-4, MHC, and troponin I. Results: CEPO administration immediately before reperfusion decreased infarction by 40% and increased ejection fraction (27%) and fractional shortening (22%), compared with untreated ischemic hearts (P < .05 each). CEPO promoted association of the EPO receptor and βcR. Furthermore, CEPO administration increased the levels of phospho-Akt in the myocardium by 59% (P < .05). A PI3K inhibitor, wortmannin, blocked the beneficial effect of CEPO on infarct size and cardiac function and attenuated the CEPO-induced Akt phosphorylation. CEPO also increased the expression of p-GATA-4, GATA-4, myosin heavy chain, and troponin I. Conclusion: A single dose of CEPO at the onset of reperfusion attenuated acute myocardial I/R injury in the mouse. CEPO-induced cardioprotection appears to be mediated through a PI3K/Akt-dependent mechanism.
Xu, Xuan; Cao, Zhijuan; Cao, Bin; Li, Jing; Guo, Lin; Que, Linli; Ha, Tuanzhu; Chen, Qi; Li, Chuanfu; and Li, Yuehua. 2009. Carbamylated Erythropoietin Protects the Myocardium From Acute Ischemia/Reperfusion Injury Through a PI3K/AKT-Dependent Mechanism. Surgery. Vol.146(3). 506-514. https://doi.org/10.1016/j.surg.2009.03.022 PMID: 19715808 ISSN: 0039-6060