Effects of rHu-EPO on myocyte apoptosis and cardiac function following acute myocardial infarction in rats

Abstract

The mechanisms of rHu-EPO attenuating the apoptosis after myocardial infraction in rats were studied. Thirty-two rats wre divided into three groups: sham operation group (Sham), acute myocardial infarction group (MI) and rHu-EPO-treated group (MI+EPO). Acute myocardial infarction model was made by ligating the anterior descending coronary artery. rHu-EPO was administered i. p. in MI+EPO group at the dose of 5 000 IU/kg body weight immediately after the ligation. Each rat in MI+EPO group received the same dose of rHu-EPO daily the next 6 days. On the 14th day all rats underwent hemodynamic measurements and then killed. The samples were examined with HE stain, immunohistochemistry technique (bcl-2, bax) and TUNEL dyeing. The results showed that hemodynamic function in MI+EPO group was much better than in MI group. The number of the cells positive for bax and TUNEL in MI+EPO group was less than that in MI group. The number of the cells positive for bcl-2 in MI+EPO group was more than that in MI group. These findings suggested that rHu-EPO could treat myocardial infarction by preventing apoptosis and attenuating post-infarction deterioration in hemodynamic function.

Keywords

recombinant human erythropoietin / myocardial infarction / apoptosis

References

[1] LindeT, WikstromB, AnderssonL G, et al. . Renal anaemia treatment with recombinant human erythropoietin increases cardiac output in patients with ischaemic heart disease. Scand J Urol Nephrol, 1996, 30115-115

[2] ChongZ Z, KangJ Q, MaieseK. Erythropoietin is a novel vascular protectant through activation of Akt1 and mitochondrial modulation of cysteine proteases. Circulation, 2002, 1062973-2973

[3] TramontanoA F, MuniyappaR, BlackA D, et al. . Erythropoietin protects cardiac myocytes from hypoxia-induced apoptosis through an Akt-dependent pathway. Biochem Biophys Res Commun, 2003, 380990-990

[4] PalojokiE, SarasteA, ErikssonA, et al. . Cardiomyocyte apoptosis and ventricular remodeling after myocardial infarction in rats. Am J Physiol Heart Circ Physiol, 2001, 2802726-2726

[5] SakanakaM, WenT C, MatsudaS, et al. . In vivo evidence that erythropoietin protect neurons from ischemic damage. Proc Natl Acad USA, 1998, 954635-4635

[6] SirenA L, FratelliM, BrinesM, et al. . Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress. Proc Natl Acad Sci USA, 2001, 984044-4044

[7] CelikM, GokmenN, ErbayraktarS, et al. . Erythropoietin prevents motor neuron apoptosis and neurologic disability in experimental spinal cord ischemic injury. Proc Natl Acad Sci USA, 2002, 992258-2258

[8] JunkA K, MammisA, SavitzS I, et al. . Erythropoietin administration protects retinal neurons from acute ischemia-reperfusion injury. Proc Natl Acad Sci USA, 2002, 9910 659-10 659

[9] CheungJ Y, MillerB A. Molecular mechanisms of erythropoietin signaling. Nephron, 2001, 87215-215