Carbamylated erythropoietin ameliorates cardiomyopathy via ERK (44/42) activation in rats with diabetic cardiomyopathy

This study aimed to investigate the potential mechanisms underlying the protective effects of carbamylated erythropoietin (CEPO) on diabetic-related myocardial fibrosis. Wistar rats were fed a high-fat/high-carbohydrate diet and intraperitoneally injected with streptozotocin to induce diabetic cardiomyopathy (DCM). The rats were then treated with recombinant human erythropoietin (rhEPO) or CEPO. The lipid and glucose levels of the rats were recorded 4 and 8 weeks after the treatment. Myocardial samples were analyzed through Massons trichrome staining and transmission electron microscopy. The expression levels of transforming growth factor-beta 1 (TGF-beta 1) and connective tissue growth factor (CTGF) were also detected. Moreover, myocardial apoptosis and extracellular signal-regulated kinase (ERK) signaling were investigated. Induction of the diabetic model significantly promoted myocardial cell apoptosis and upregulated the protein expression levels of TGF-beta 1 and CTGF. Treatment with CEPO or rhEPO decreased the number of apoptotic cells, ameliorated the dissolution of myocardial myofilaments and damage of mitochondria, and downregulated TGF-beta 1 and CTGF expression levels in the myocardium of diabetic rats. Furthermore, CEPO increased ERK (44/42) protein expression levels in the hearts of diabetic rats. Overall, it was found that myocardial fibrosis may contribute to myocardial injury in diabetes mellitus and that CEPO might protect the myocardium of diabetic rats against fibrosis through the ERK (44/42) signaling pathway.