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AAV-PGIS Gene Transfer Improves Hypoxia-Induced Pulmonary Hypertension in Mice

Takashi Kawakami

Masaharu Kataoka

Toru Satoh

K. Fukuda

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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.