Osthole improves pulmonary artery hypertension by inducing apoptosis in pulmonary artery smooth muscle cells

Objectives The objectives of this study were to explore the effect of Osthole (Ost) on apoptosis in pulmonary artery smooth muscle cells (PASMCs) and investigate the potential mechanism of this effect. Methods Rats were injected subcutaneously with monocrotaline (MCT) to establish a PAH model, and Ost were intragastrically administrated from day 1 to day 35. After 35 days administration, the mean pulmonary artery pressure and lung weight index were measured. HE and TUNEL staining were used to observe the morphology of pulmonary artery and the apoptosis of PASMCs. In addition, the apoptosis of PASMCs were detected by flow cytometry in cultured PASMCs. The proteins of Bax and Bcl-2, and the levels of p-ASK1 and cleaved caspase 3 were measured by Western blot. Key findings Ost decreased the mean pulmonary artery pressure and lung weight index in MCT-induced rats, and promoted apoptosis in PASMCs in MCT-induced rats and PDGF-BB stimulated PASMCs. Ost increased the ratio of Bax/Bcl-2 and the levels of p-ASK1, cleaved caspase 3 in MCT-induced rats and PDGF-BB stimulated PASMCs. Conclusion Ost promoted apoptosis in PASMCs in vivo and in vitro, and the mechanism may be associated with upregulation of ASK1 and the Bax/Bcl-2-caspase 3 signalling pathway.