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

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.