Gene delivery to ischemic cardiomyocytes using dexmethasone conjugated polyethylenimine

Abstract

Dexamethasone is a potent glucocorticoid with anti-inflammatory effect. It protects ischemic cardiomyocytes from apoptosis. To apply this effect to ischemic disease gene therapy, dexmethasone conjugated polyethylenimine (PEI2K) (PEI-Dexa) was evaluated as a gene carrier to cardiomyocyte. PEI-Dexa had higher transfeciton efficiency into H9C2 rat cardiomyocytes than high molecular polyethylenimine (PEI25K). The cytotoxicity of PEI-Dexa was lower than that of PEI25K. PEI-Dexa reduced the caspase-3 activity compared to PEI or control, suggesting that PEI-Dexa has cytoprotective effect aginst hypoxi-induced apoptosis of cardiomyocytes. Heme oxygenase-1 (HO-1) has an anti-apoptotic gene and HO-1 was used as a model gene. However, it was reported that overexpression of HO-1 in normal cell had deleterious effect such as tumor growth. To limit HO-1 expression to hypoxic cells, hypoxia inducible HO-1 plasmid, pEPO-SV-HO-1 was constructed. In transfection assay. PEI-Dexa delivered pEpo-SV-HO-1 into H9C2 cells effectively and HO-1 expression was induced under hypoxia. In conclusion, PEI-Dexa in combination with pEpo-SV-HO-1 may be useful for ischemic disease gene therapy as a gene carrier adn also and anti-apoptotic reagent.