{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T07:38:03Z","timestamp":1793086683367,"version":"4.5.0"},"reference-count":25,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2012,9,24]],"date-time":"2012-09-24T00:00:00Z","timestamp":1348444800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cardiovasc Pharmacol Ther"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:p>\n                    Prostaglandin I\n                    <jats:sub>2<\/jats:sub>\n                    (PGI\n                    <jats:sub>2<\/jats:sub>\n                    ) plays an important role in the clinical treatment of pulmonary arterial hypertension (PAH). However, the administration of PGI\n                    <jats:sub>2<\/jats:sub>\n                    involves continuous intravenous infusion using an indwelling catheter, which limits the patient\u2019s quality of life and increases the risk of infection. We therefore investigated whether human PGI\n                    <jats:sub>2<\/jats:sub>\n                    synthase (hPGIS) gene transfer using an adeno-associated virus (AAV) vector is still effective in a mouse model of PAH and tested for differences in the therapeutic efficacy of PAH among AAV serotypes. The PAH was induced by subjecting mice to hypoxia (10% O\n                    <jats:sub>2<\/jats:sub>\n                    ). Type 1 AAV expressing hPGIS (AAV1-hPGIS) or type 2 AAV expressing hPGIS (AAV2-hPGIS) was injected into the thigh muscle of mice. Both vectors expressing hPGIS produced strong hPGIS protein expression in the mouse thigh skeletal muscles after 8 weeks of hypoxia. The administration of AAV1-hPGIS or AAV2-hPGIS also significantly inhibited the hypoxia-induced increase in right ventricular systolic pressure, the ratio of right ventricular weight to body weight (RV\/BW), and the ratio of RV weight to left ventricular plus septal weight (RV\/LV + S), and significantly attenuated the hypoxia-induced increase in medial wall thickness of peripheral pulmonary arteries. Furthermore, there were no significant differences in the degree of amelioration in RV systolic pressure, RV\/BW, RV\/LV + S, and percentage of wall thickness of peripheral pulmonary arteries between AAV1-hPGIS and AAV2-hPGIS administrations. In conclusion, we revealed that type 1 and type 2 AAV are equally effective for the treatment of PAH in a hypoxia-induced mouse model. Gene-transfer therapy using AAV expressing hPGIS is, therefore, a potential therapeutic breakthrough for PAH.\n                  <\/jats:p>","DOI":"10.1177\/1074248412457046","type":"journal-article","created":{"date-parts":[[2012,9,24]],"date-time":"2012-09-24T23:20:16Z","timestamp":1348528816000},"page":"54-59","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["Gene Transfer Therapy by Either Type 1 or Type 2 Adeno-Associated Virus Expressing Human Prostaglandin I\n                    <sub>2<\/sub>\n                    Synthase Gene is Effective for Treatment of Pulmonary Arterial Hypertension"],"prefix":"10.1177","volume":"18","author":[{"given":"Masaharu","family":"Kataoka","sequence":"first","affiliation":[{"name":"Department of Cardiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan"},{"name":"Department of Medicine, Division of Cardiology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kawakami","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Tamura","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Yoshino","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Satoh","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Tanabe","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiichi","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2012,9,24]]},"reference":[{"key":"bibr1-1074248412457046","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-107-2-216"},{"key":"bibr2-1074248412457046","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-115-5-343"},{"key":"bibr3-1074248412457046","doi-asserted-by":"publisher","DOI":"10.1378\/chest.114.3_Supplement.237S"},{"key":"bibr4-1074248412457046","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.102.22.2781"},{"key":"bibr5-1074248412457046","doi-asserted-by":"publisher","DOI":"10.1038\/263663a0"},{"key":"bibr6-1074248412457046","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197905173002006"},{"key":"bibr7-1074248412457046","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.102.16.2005"},{"key":"bibr8-1074248412457046","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(99)00320-4"},{"key":"bibr9-1074248412457046","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(84)91452-1"},{"key":"bibr10-1074248412457046","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-112-7-485"},{"key":"bibr11-1074248412457046","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.70.4.366"},{"key":"bibr12-1074248412457046","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-121-6-199409150-00003"},{"key":"bibr13-1074248412457046","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199602013340504"},{"key":"bibr14-1074248412457046","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199801293380501"},{"key":"bibr15-1074248412457046","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000029100.82385.58"},{"key":"bibr16-1074248412457046","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(02)02012-0"},{"key":"bibr17-1074248412457046","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)24019-5"},{"key":"bibr18-1074248412457046","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(99)00312-5"},{"key":"bibr19-1074248412457046","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020204"},{"key":"bibr20-1074248412457046","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.165.6.2106079"},{"key":"bibr21-1074248412457046","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.09.039"},{"key":"bibr22-1074248412457046","doi-asserted-by":"publisher","DOI":"10.1038\/nm1358"},{"key":"bibr23-1074248412457046","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)77740-0"},{"issue":"12","key":"bibr24-1074248412457046","first-page":"1589","volume":"12","author":"During 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