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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)656-661
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume363
Issue number3
DOIs
Publication statusPublished - 2007 Nov 23

Fingerprint

Gene transfer
Dependovirus
Viruses
Pulmonary Hypertension
Genes
Level control
Epoprostenol
Muscle
Hypoxia
Animals
Thigh
Intravenous Administration
Pulmonary Artery
Up-Regulation
Animal Models
Blood Pressure
Muscles
Survival

Keywords

  • AAV
  • Gene transfer
  • PGIS
  • Pulmonary hypertension

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

AAV-PGIS gene transfer improves hypoxia-induced pulmonary hypertension in mice. / Kawakami, Takashi; Kanazawa, Hideaki; Satoh, Toru; Ieda, Masaki; Ieda, Yasuyo; Kimura, Kensuke; Mochizuki, Hideki; Shimada, Takashi; Yokoyama, Chieko; Ogawa, Satoshi; Tanabe, Tadashi; Fukuda, Keiichi.

In: Biochemical and Biophysical Research Communications, Vol. 363, No. 3, 23.11.2007, p. 656-661.

Research output: Contribution to journalArticle

Kawakami, T, Kanazawa, H, Satoh, T, Ieda, M, Ieda, Y, Kimura, K, Mochizuki, H, Shimada, T, Yokoyama, C, Ogawa, S, Tanabe, T & Fukuda, K 2007, 'AAV-PGIS gene transfer improves hypoxia-induced pulmonary hypertension in mice', Biochemical and Biophysical Research Communications, vol. 363, no. 3, pp. 656-661. https://doi.org/10.1016/j.bbrc.2007.09.039
Kawakami, Takashi ; Kanazawa, Hideaki ; Satoh, Toru ; Ieda, Masaki ; Ieda, Yasuyo ; Kimura, Kensuke ; Mochizuki, Hideki ; Shimada, Takashi ; Yokoyama, Chieko ; Ogawa, Satoshi ; Tanabe, Tadashi ; Fukuda, Keiichi. / AAV-PGIS gene transfer improves hypoxia-induced pulmonary hypertension in mice. In: Biochemical and Biophysical Research Communications. 2007 ; Vol. 363, No. 3. pp. 656-661.
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