AIM To investigate the role of acid sphingomyelinase (ASM)/ceramide (Cer) in proliferation, apoptosis and phenotype switch of vascular smooth muscle cells (VSMCs) in the femoral artery (FA) of simulated weightless rats.

METHODS Rats were subject to hindlimb-unloaded tail-suspension (HU) to simulate the hemodynamic effect of weightlessness on FA. The expressions of ASM and Cer, and representative markers of proliferation, apoptosis and phenotype switch of VSMCs were examined by Western blotting and immunohistochemistry (IHC).

RESULTS The protein expressions of proliferating cell nuclear antigen (PCNA), cysteinyl aspartate specific proteinase 3 (Caspase3), B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) along with the ratio of Vimentin to α-smooth muscle actin (α-SMA) in FA were increased significantly by HU (P<0.05). Meanwhile, the ASM protein and Cer abundance in FA of HU rats were higher than those in CON (P<0.05). Furthermore, desipramine (Dpm) or doxepin hydrochloride (DOX), the two inhibitors of ASM, reversed Bax expression and the vimentin/α-SMA ratio in FA of HU rats substantially (P<0.05). Notably, the expression of Bcl-2 in FA of HU rats showed a tendency to be increased after Dpm treatment and was increased significantly after DOX gavage.

CONCLUSION Simulated weightlessness modulates the proliferation and apoptosis of VSMCs in FA, promoting the phenotype switch from a contractile to synthetic state, which is attributable to the over-activation of the ASM/Cer pathway.