Treatment with curcumin significantly reversed the detrimental effects of rapamycin. - GreenMedInfo Summary

Although drug-eluting stents (DES) effectively improve the clinical efficacy of percutaneous coronary intervention, a high risk of late stent thrombosis and in-stent restenosis also exists after DES implantation. Anti-smooth muscle proliferation drugs, such as rapamycin, coating stents not only inhibit the growth of vascular smooth muscle cells but also inhibit vascular endothelial cells and delay the re-endothelialization. Therefore, the development of an ideal agent that protects vascular endothelial cells from rapamycin-eluting stents is of great importance for the next-generation of DES. In the present study, we demonstrated that rapamycin significantly inhibited the growth of rat aortic endothelial cells (RAECs) in both a dose- and time-dependent manner in vitro. Cell apoptosis was increased and migration was decreased by rapamycin treatments in RAECs in vitro. Surprisingly, treatment with curcumin, an active ingredient of turmeric, significantly reversed these detrimental effects of rapamycin. Moreover, curcumin increased the expression of vascular nitric oxide synthases (eNOS) which was decreased by rapamycin. Furthermore, caveolin-1, the inhibitor of eNOS, was decreased by curcumin. Knockdown of eNOS by small interfering RNA significantly abrogated the protective effects of curcumin. Taken together, our results suggest that curcumin antagonizes the detrimental effect of rapamycin on aortic endothelial cells in vitro through up-regulating eNOS. Therefore, curcumin is a promising combined agent for the rescue of DES-induced re-endothelialization delay.