title: Suppression of the expression of hypoxia-inducible factor-1α by RNA interference alleviates hypoxia-induced pulmonary hypertension in adult rats.
abstract: Hypoxia-inducible factor-1α (HIF-1α) has been implicated in the pathogenesis of hypoxic pulmonary hypertension (PH). However, the potential clinical value of HIF-1α as a therapeutic target in the treatment of PH has not yet been evaluated. In this study, an animal model of hypoxia-induced PH was established by exposing adult rats to 10% O2 for 3 weeks, and the effects of the lentivirus-mediated delivery of HIF-1α short hairpin RNA (shRNA) by intratracheal instillation prior to exposure to hypoxia on the manifestations of hypoxia-induced PH were assessed. The successful delivery of HIF-1α shRNA into the pulmonary arteries effectively suppressed the hypoxia-induced upregulation of HIF-1α, accompanied by the prominent attenuation the symptoms associated with hypoxia-induced PH, including the elevation of pulmonary arterial pressure, hypertrophy and hyperplasia of pulmonary artery smooth muscle cells (PASMCs), as well as the muscularization of pulmonary arterioles. In addition, the knockdown of HIF-1α in cultured rat primary PASMCs significantly inhibited the hypoxia-induced acceleration of the cell cycle and the proliferation of the PASMCs, suggesting that HIF-1α may be a direct mediator of PASMC hyperplasia in hypoxia-induced PH. In conclusion, this study demonstrates the potent suppressive effects of HIF-1α shRNA on hypoxia-induced PH and PASMC hyperplasia, providing evidence for the potential application of HIF-1α shRNA in the treatment of hypoxic PH.
authors.affiliation: Department of Ultrasound Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Ultrasound Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Shi
authors.affiliation: Department of Ultrasound Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Liping
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Ultrasound Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Ultrasound Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Xiaona
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Ultrasound Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Baosheng
authors.initials: B
authors.lastname: Guo
authors.affiliation: Department of Ultrasound Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Ren
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism*; D000860:Hypoxia / Q000235:genetics* / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism*; D011651:Pulmonary Artery / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D066253:Vascular Remodeling / Q000235:genetics
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering