Recombinant human erythropoietin pretreatment attenuates myocardial infarct size: a possible mechanism involves heat shock Protein 70 and attenuation of nuclear factor-kappaB.
Erythropoietin (EPO), known for its role in stimulating erythropoiesis, has recently been shown to have a cardio-protective effect in animal models of myocardial ischemia-reperfusion (I-R) injury. The mechanism of the cardio-protective effect of EPO is unclear. Part of the mechanism for EPO-induced cardio-protection may involve inhibition of myocardial apoptosis and preservation of ATP levels in the ischemic myocardium. We studied the expression of heat shock protein 70 (Hsp70) and its possible links to the cardio-protective effect of EPO. A rat model of myocardial I-R injury was established by ligating the left descending coronary artery for 30 min and then reperfusing for 2 hr. Recombinant human EPO (rhEPO) was injected ip 24 hr before the ligation. The myocardial infarct size and the area at risk of ischemia were measured by staining with triphenyltetrazolium chloride (TTC) and Evans blue dye. Expression of Hsp70 in the left ventricle was analyzed by ELISA and that of nuclear factor-kappaB (NF-kappaB) was analyzed by electrophoretic mobility shift assay (EMSA). The results showed that a single ip injection of 3,000 units/kg of rhEPO at 24 hr pre-ligation enhanced the expression of Hsp70 and diminished the expression of NF-kappaB in rat myocardium, and that the myocardial infarct induced by I-R injury was remarkably reduced in size, compared to control rats that received an ip saline injection at 24 hr pre-ligation.
Xu
Biao
B
Department of Cardiothoracic Surgery, Jingling Hospital, Nanjing University Medical School, Nanjing, People's Republic of China. xubiao3000@msn.com
Dong
Guo-hua
GH
Liu
Hong
H
Wang
Yan-qing
YQ
Wu
Hai-wei
HW
Jing
Hua
H
D000818:Animals; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D004921:Erythropoietin / Q000627:therapeutic use*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins
D018840:HSP70 Heat-Shock Proteins; D016328:NF-kappa B; D011994:Recombinant Proteins; D004921:Erythropoietin