Inhibition of survivin promotes pulmonary arterial smooth muscle cell apoptosis in high blood flow-induced pulmonary arterial hypertension in rats

The precise pathogenesis of high pulmonary blood flow-induced pulmonary arterial hypertension (PAH) remains unclear. The purpose of this study was to explore the expression and function of survivin in pulmonary arterial smooth muscle cell (PASMC) in a rat model of high pulmonary blood flow-induced PAH. Sprague-Dawley (SD) rats were randomly divided into the following groups: Control group, Sham group, Shunt group, and Shunt+siRNA group. The rats in the Shunt and Shunt+siRNA groups were used to establish the high pulmonary blood flow-induced PAH model. The pulmonary arteries were isolated for the primary culture of PASMCs. PASMC in the Shunt+siRNA group underwent siRNA-survivin transfection. The survivin gene and protein expression levels were analyzed, and PASMC proliferation and apoptosis were assessed in each group. We found that survivin gene and protein expression levels were increased in PASMCs in the Shunt and Shunt+siRNA groups compared with the Control and Sham groups (P<0.05). PASMC proliferation and apoptosis were significantly increased and inhibited, respectively, in the Shunt group relative to the Control and Sham groups (P<0.05). In the Shunt+siRNA group, survivin gene and protein expression significantly decreased, PASMC apoptosis increased, and proliferation was inhibited relative to that in the Shunt group (P<0.05). Our results indicate that survivin is expressed in PASMC in a rat model of high pulmonary blood flow-induced PAH and both attenuate Kv1.5 and Kv2.1 channel expression and inhibits caspase-3 and caspase-9 activity. Targeting survivin may represent a potent therapeutic measure to promote PASMC’s apoptosis and inhibit its proliferation in PAH, helping to reverse pulmonary arterial remodeling.