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Epoxyeicosatrienoic acids (EETs), products of the cytochrome P450 epoxygenase metabolism of arachidonic acid, are potent vasodilators that possess anti-inflammatory and other protective properties in endothelial cells. We investigated whether gene delivery with the human cytochrome P450 epoxygenase 2J2 (CYP2J2) ameliorates monocrotaline (MCT)-induced pulmonary hypertension in rats. Significant pulmonary hypertension developed 3 weeks after the administration of MCT, but gene therapy with CYP2J2 significantly attenuated the development of pulmonary hypertension and pulmonary vascular remodeling, without causing changes in systemic arterial pressure or heart rate. These effects were associated with increased pulmonary endothelial NO synthase (eNOS) expression and its activity, inhibition of inflammation in the lungs, and transforming growth factor (TGF)-\u03b2\/type II bone morphogenetic protein receptor (BMPRII)-drosophila mothers against decapentaplegic proteins (Smads) signaling. Collectively, these data suggest that gene therapy with CYP2J2 may have potential as a novel therapeutic approach to this progressive and oftentimes lethal disorder.<\/jats:p>","DOI":"10.1165\/rcmb.2009-0161oc","type":"journal-article","created":{"date-parts":[[2010,1,29]],"date-time":"2010-01-29T22:59:42Z","timestamp":1264805982000},"page":"740-749","source":"Crossref","is-referenced-by-count":28,"title":["Gene Delivery of Cytochrome P450 Epoxygenase Ameliorates Monocrotaline-Induced Pulmonary Artery Hypertension in Rats"],"prefix":"10.1093","volume":"43","author":[{"given":"Changlong","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Gene Therapy Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luyun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Internal 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