Prostacyclin synthase gene transfer inhibits neointimal formation in rat balloon-injured arteries without bleeding complications.

Abstract

This study was designed to compare the effects of prostacyclin synthase (PCS) gene transfer with those of a systemic infusion of beraprost sodium (BPS), a prostacyclin analogue, on vascular smooth muscle cell (VSMC) proliferation and neointimal formation after arterial injury. PCS gene (3 or 30 micrograms) was transfected into rat balloon-injured carotid arteries by a non-viral lipotransfection method. BPS (100 or 300 micrograms/kg/day) was subcutaneously infused with osmotic pumps after the injury. LacZ gene (30 micrograms) was used as a control. VSMC proliferation was estimated by the bromodeoxyuridine (BrdU) index (BrdU-positive nuclei/total nuclei) at day 7. Neointimal formation was evaluated at day 14. Each treatment group had six rats. PCS gene transfer prevented the increase in intimal/medial area ratio (3 micrograms: 46.6%, 30 micrograms: 61.1% reduction; P < 0.05, P < 0.01, respectively), as did BPS 300 micrograms/kg/day (49.8% reduction; P < 0.05). BPS 100 micrograms/kg/day, however, had no effects on the ratio. PCS gene transfer and BPS 300 micrograms/kg/day significantly suppressed the BrdU index. BPS 300 micrograms/kg/day group had more frequent hematoma and longer bleeding time. There were no significant differences in blood pressure, heart rate, or urinary volume among all groups. Both PCS gene transfer and BPS 300 micrograms/kg/day reduced neointimal formation after arterial injury by inhibiting VSMC proliferation. PCS gene transfer may be a safer therapeutic modality against neointimal formation than a systemic infusion of BPS because the former method resulted in fewer bleeding complications.