Carbamylated Erythropoietin Promotes Coronary Neovascularization through Extracellular Signal Regulated Kinase Pathway in Diabetic Rats with Myocardial Infarction

Abstract

To investigate whether carbamylated erythropoietin can influence the coronary collateral circulation via extracellular signal regulated kinase 1/2 signaling pathway. A diabetic rat model was established. Vascular endothelial growth factor, angiotensin-I and phosphorylated-extracellular signal regulated kinase 1/2 expression were observed along with changes in hemodynamics and infarct area. The results showed that left ventricular diastolic pressure, left ventricular end diastolic pressure, maximum rate of left ventricular pressure rise, heart rate, (left ventricular systolic pressure-left ventricular diastolic pressure#)* heart rate, microvessel density and vascular endothelial growth factor were significantly decreased and the percentage of myocardial infarct size, the levels of prostacyclin, endothelin 1, angiotensin II, von Willebrand factor, phosphorylated-fibroblast growth factor receptor 2, phosphorylated-phospholipase C gamma and phosphorylated-extracellular signal regulated kinase 1/2 were significantly increased in other groups compared with control group (p<0.05). Left ventricular diastolic pressure, left ventricular end diastolic pressure, maximum rate of left ventricular pressure rise, heart rate and (left ventricular systolic pressureleft ventricular diastolic pressure#)* heart rate were significantly increased in carbamylated erythropoietin group and significantly decreased in carbamylated erythropoietin+PD98059 group compared with the sham group (p<0.05). However, the myocardial infarction size and the levels of prostacyclin, endothelin 1, angiotensin II and von Willebrand factor were significantly decreased and the microvessel density, vascular endothelial growth factor, angiotensin-1, phosphorylated-fibroblast growth factor receptor 2, phosphorylatedphospholipase C gamma and phosphorylated-extracellular signal regulated kinase 1/2 were significantly increased in carbamylated erythropoietin and carbamylated erythropoietin+PD98059 groups compared with the sham group (p<0.05). Amino glycosylated erythropoietin was able to improve the hemodynamics of diabetic infarct rats and there was also an extracellular signal regulated kinase 1/2 conduction pathway in the neovascularization of diabetic infarct rats. This provides a new target for future clinical use to reduce myocardial damage caused by myocardial infarction.