AAV-PGIS gene transfer improves hypoxia-induced pulmonary hypertension in mice

Takashi Kawakami, Hideaki Kanazawa, Toru Satoh, Masaki Ieda, Yasuyo Ieda, Kensuke Kimura, Hideki Mochizuki, Takashi Shimada, Chieko Yokoyama, Satoshi Ogawa, Tadashi Tanabe, Keiichi Fukuda

研究成果: Article査読

12 被引用数 (Scopus)

抄録

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. PH was induced by subjecting mice to 10% O2. Type 1-AAV-hPGIS was injected into the left thigh muscle after 24 h. 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. This study demonstrated that AAV-hPGIS administration was effective in treating PH and prolonging survival.

本文言語English
ページ(範囲)656-661
ページ数6
ジャーナルBiochemical and Biophysical Research Communications
363
3
DOI
出版ステータスPublished - 2007 11月 23

ASJC Scopus subject areas

  • 生物理学
  • 生化学
  • 分子生物学
  • 細胞生物学

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