YM155, a selective survivin inhibitor, reverses chronic hypoxic pulmonary hypertension in rats via upregulating voltage-gated potassium channels

Clin Exp Hypertens. 2015;37(5):381-7. doi: 10.3109/10641963.2014.987390. Epub 2015 Apr 9.

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.

Keywords: Hypoxia; YM155; potassium channels; pulmonary hypertension; survivin.

MeSH terms

  • Animals
  • Chronic Disease
  • Disease Models, Animal
  • Gene Expression Regulation*
  • Hypertension, Pulmonary / complications
  • Hypertension, Pulmonary / drug therapy
  • Hypertension, Pulmonary / genetics*
  • Hypoxia / etiology
  • Hypoxia / genetics*
  • Hypoxia / metabolism
  • Imidazoles / therapeutic use*
  • Male
  • Microtubule-Associated Proteins / antagonists & inhibitors*
  • Microtubule-Associated Proteins / biosynthesis
  • Microtubule-Associated Proteins / genetics
  • Muscle, Smooth, Vascular / metabolism*
  • Muscle, Smooth, Vascular / physiopathology
  • Naphthoquinones / therapeutic use*
  • Patch-Clamp Techniques
  • Potassium Channels, Voltage-Gated / biosynthesis
  • Potassium Channels, Voltage-Gated / genetics*
  • Pulmonary Wedge Pressure
  • RNA / genetics
  • Rats
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction
  • Survivin

Substances

  • Birc5 protein, rat
  • Imidazoles
  • Microtubule-Associated Proteins
  • Naphthoquinones
  • Potassium Channels, Voltage-Gated
  • Survivin
  • RNA
  • sepantronium