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