Conference: 2010 International PHA Conference and Scientific Sessions
Release Date: 06.24.2010
Presentation Type: Abstracts
Kawakami T1, Kataoka M1, Satoh T1, Fukuda K2.
1. Cardiology Division, Department of Internal Medicine, Kyorin University, Japan
2. Cardiology Division, Department of Internal Medicine, Keio University, Japan
BACKGROUND: Although prostaglandin I2 is used to treat pulmonary hypertension (PH), continuous intravenous administration is necessary. We investigated whether human PGIS (hPGIS) gene transfer using adeno-associated virus (AAV) vector was effective in treating an animal model of PH.
METHODS: After 24 hours of exposure to hypoxia, AAV1-hPGIS was administered into the left thigh muscle by single injection. The vehicle (0.9% saline) was injected into the same site in PH and control groups. Hemodynamics were measured at 8 weeks.
RESULTS: Significant PH was induced at 8 weeks, but AAV-hPGIS administration significantly inhibited the increase in RV systolic pressure. PH-induced BNP up-regulation in the RV was reduced to the control level. The severe medial thickening of pulmonary arteries in PH was significantly suppressed by AAV-hPGIS. The hPGIS gene was detected only on the injected side. No pathological changes were observed at the injected site. At 24 weeks, all PH mice were deceased, but 47% of AAV-hPGIS-treated mice survived.
CONCLUSIONS: This study demonstrated that AAV-hPGIS administration was effective in treating PH and prolonging survival.