NEW TREATMENT FOR PULMONAY HYPERTENSION

点击翻译按钮获取中文摘要

(1)Naked plasmid encoding the prostacyclin synthase (PGIS) gene was injected into the thigh muscle every 7 days from 1 week and 4weeks after monocrotaline injection in rats. PGIS gene transfer increased intramuscular and serum 6-keto-prostaglandin F2-alpha, a stable metabolite of prostacyclin. Repeated PGIS gene transfers significantly reduced pulmonary arterial pressure and ameliorated right ventricular hypertrophy and pulmonary arterial remodeling in monocrotaline-treated rats. Furthermore, survival rate was significantly improved by repeated PGIS gene transfers.(2)In normal rats, 3% of intravenously implanted bone marrow-derived mononuclear cells (BM-MNCs) accumulated in the lung 1 day after cell transplantation. Two weeks after cell transplantation, only 1 % of tranplnted BM-MNCs were detected in the lung. In contrast, the rate of lung distribution of transplanted BM-MNCs were remarkably increased in monocrotalin-induced pulmonary hypertension rats (10% and 6% at days 1 and 14, respectively).(3)We established BM-MNC line, which overexpresses PGIS gene and produces prostacyclin, by using a retroviral vector-mediated gene transfer of PGIS.(4)Transplantation of PGIS-overexpressing BM-MNCs significantly reduced pulmonary arterial pressure and ameliorated right ventricular hypertrophy in monocrotaline-induced pulmonary hypertension rats.