Vitamin E antagonizes oxLDL‐induced CD36 over‐expression in monocytes

Uptake and accumulation of oxLDL by scavenger receptors converts monocytes, macrophages and vascular smooth muscle cells into foam cells, a key process during the development of atherosclerosis. Several pro‐atherogenic triggers exist that lead to over‐expression of the CD36 scavenger receptor. In this study we investigate the signaling pathways involved in up‐regulation of CD36, and check at which site vitamin E (alpha‐tocopherol) can interfere with this event. In monocytes, CD36 over‐expression is induced by oxLDL and alpha‐tocopherol antagonizes oxLDL by normalizing oxLDL‐stimulated cellular signaling events. Over‐expression of the CD36 scavenger receptor occurs also after inhibition of the proteasome by the anti‐retroviral protease inhibitor, ritonavir. CD36 over‐expression and proteasome inhibition after ritonavir treatment can be normalized by alpha‐tocopherol. Interestingly, the phosphorylated form of alpha‐tocopherol, alpha‐tocopheryl‐phosphate, led even in non‐stimulated THP‐1 monocytes to inhibition of CD36 expression, whereas in these cells alpha‐tocopherol itself reduced only weakly. The higher potency of alpha‐tocopheryl‐phosphate may be due to a better uptake of the molecule and to its intracellular hydrolysis, providing more alpha‐tocopherol to sensitive sites. Alternatively, a direct effect of the alpha‐tocopheryl‐phosphate ester on specific cellular targets may be considered.