Objective To explore the effect of connexin 43(Cx43)on proliferation and apoptosis of vascular smooth muscle cells under simulated microgravity.Methods Human aortic smooth muscle cells(HASMCs)were divided into normal gravity group(Con group)and simulated microgravity group(SMG group),and cell model under simulated microgravity was established.After 48 h of cell culture,qRT-PCR and Western blotting were used to detect the expression of Cx43 in HASMCs.After adding the connexin inhibitor 18-alpha-glycyrrhetinic acid(18α-GA),the two groups were divided into Con group,normal gravity plus inhibitor group,SMG group,and simulated microgravity plus inhibitor group(SMG+inhibitor group).Western blotting was used to detect the effects of simulated microgravity on the expression levels of proliferating cell nuclear antigen(PCNA),B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(BAX)and other proteins in HASMCs.The proliferation capacity of HASMCs was detected by EdU,and the apoptosis of HASMCs was detected by flow cytometry.The expression of Cx43 in carotid smooth muscle cells of tail-suspended rats was detected by immunofluorescence.Results After 48 h of simulated microgravity culture in HASMCs,the mRNA and protein expression levels of Cx43 in HASMCs significantly increased compared with Con group(P<0.05).The expression levels of PCNA in SMG+inhibitor group decreased significantly(P<0.05),Bcl-2 protein levels significantly decreased(P<0.05),and BAX level significantly increased(P<0.05).Compared with SMG group,the proportion of EdU positive cells in HASMCs in SMG+inhibitor group decreased significantly(P<0.05).The results of flow cytometry showed that the apoptosis rate of HASMCs was significantly increased in SMG+inhibitor group(P<0.05).The immunofluorescence results of tail-suspended rats showed that Cx43 expression in carotid smooth muscle cells of tail-suspended rats increased significantly compared with that of normal rats.Conclusion Cx43 promotes the proliferation of HASMCs and inhibits the apoptosis of HASMCs under simulated microgravity.