Inhibitory effect of PMC, a potent hydrophilic α-tocopherol derivative, on vascular smooth muscle cell proliferation: the pivotal role of PKC-α translocation.

Content: Vascular smooth muscle cells (VSMCs) play a major role in the pathogenesis of atherosclerosis and restenosis, and thus the excessive proliferation of VSMCs contributes to neointimal thickening during atherosclerosis and restenosis. PMC (2,2,5,7,8-pentamethyl-6-hydroxychromane) is the most potent hydrophilic derivative of the alpha-tocopherols; it acts as a potent anti-inflammatory and free-radical scavenger.

Objective: The present study was designed to examine the inhibitory mechanisms of PMC in VSMC proliferation.

Materials And Methods: VSMC proliferation and cytotoxicity were measured by MTT and LDH assays, respectively. The cell cycle and translocation of PKC-alpha in VSMCs were used by flow cytometry and confocal microscope, respectively. To detect PKC-alpha translocation and activation in VSMCs, immunoblotting was performed in the present study.

Results: In this study, we demonstrate an anti-proliferative effect of PMC in VSMCs. Concentration-dependent inhibition of serum-induced VSMC proliferation was observed in PMC (20 and 50 muM)-treated cells. PMC pretreatment also arrested VSMC cell cycle progression at the G2/M phase. Furthermore, PMC exhibited obvious inhibitory effects on phorbol 12-myristate 13-acetate (PMA)-induced protein kinase C (PKC)-alpha translocation and phospho-(Ser/Thr) substrate phosphorylation.

Discussion And Conclusion: The inhibitory mechanisms of PMC on VSMC proliferation is mediated, at least in part, by inhibition of PKC-alpha translocation and causes cell cycle arrest in the G2/M phase. PMC treatment may represent a novel approach for lowering the risk of or improving function in abnormal VSMC proliferation-related vascular diseases.