Inhibitory effect of carbon monoxide on proliferation of rat pulmonary artery smooth muscle cells under anoxia

AIM: To investigate the effect of endogenous and exogenous carbon monoxide on the proliferation of pulmonary artery smooth muscle cells under anoxic condition. METHODS: Primary culture of rat PASMCs were passed every 3 days, the 3-5 passages were used. PASMCs were divided into 5 groups, cultured under normoxia and hypoxia and treated with HO inducer hemin, CO scavenger bovine hemoglobin (Hb) and exogenous carbon monoxide (CO), respectively. After 48 hours incubation under the conditions mentioned above, the following assay were carried out: 1) the MTT colorimetric assay and immunocytochemical staining were used to study the energy metabolism and the expression of proliferating cell nuclear antigen (PCNA) in PASMCs. 2) flow cytometry was used to analyze the cell cycle of PASMCs. RESULTS: In comparison with the control group, the value of MTT colorimetric assay was higher, the immunocytochemical staining of PCNA was stronger and the percentages of PASMCs in S and G₂M phases in the anoxia group were higher (P＜0.01). After treatment with hemin and CO, the above indexes were decreased (P＜0.01 or P＜0.05). But treatment with Hb made the above indexes increased (P＜0.01 or P＜0.05). CONCLUSION: The endogenous CO suppress the proliferation of PASMC in an autocrine way. Both the induction of endogenous CO by hemin and the treatment with exogenous CO could suppress the rat PASMCs' proliferation under anoxic condition.