title: YM155, a selective survivin inhibitor, reverses chronic hypoxic pulmonary hypertension in rats via upregulating voltage-gated potassium channels.
abstract: To test the hypothesis that chronic hypoxic pulmonary hypertension (CH-PH) is associated with increased survivin and decreased voltage-gated potassium (KV) channels expression in pulmonary arteries, rats were randomized as: normoxia (N); normoxia + YM155, survivin suppressor (NY); hypoxia (H); hypoxia + YM155 (HY). HY group had significantly reduced pulmonary arterial pressure, right ventricular weight and right ventricular hypertrophy compared with H group. Survivin mRNA and protein were detected in pulmonary arteries of rats with CH-PH, but not rats without CH-PH. YM155 downregulated survivin protein and mRNA. KV channel expression and activity were upregulated after YM155 treatment. Survivin may play a role in the pathogenesis of CH-PH.
authors: Department of Respiratory Medicine, General Hospital of PLA Air Force , Beijing , China .
authors: Zaiwen
authors: Z
authors: Fan
authors: Bo
authors: B
authors: Liu
authors: Shuai
authors: S
authors: Zhang
authors: Huiguo
authors: H
authors: Liu
authors: Yang
authors: Y
authors: Li
authors: Dong
authors: D
authors: Wang
authors: Ying
authors: Y
authors: Liu
authors: Jian
authors: J
authors: Li
authors: Ning
authors: N
authors: Wang
authors: Yi
authors: Y
authors: Liu
authors: Bo
authors: B
authors: Zhang
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006976:Hypertension, Pulmonary / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D000860:Hypoxia / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000503:physiopathology; D009285:Naphthoquinones / Q000627:therapeutic use*; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000096:biosynthesis / Q000235:genetics*; D011669:Pulmonary Wedge Pressure; D012313:RNA / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D000077022:Survivin
chemical_list: C516989:Birc5 protein, rat; D007093:Imidazoles; D008869:Microtubule-Associated Proteins; D009285:Naphthoquinones; D024642:Potassium Channels, Voltage-Gated; D000077022:Survivin; D012313:RNA; C523798:sepantronium
keywords: Hypoxia; YM155; potassium channels; pulmonary hypertension; survivin