Resveratrol Derivative, Trans-3, 5, 4'-Trimethoxystilbene, Prevents the Developing of Atherosclerotic Lesions and Attenuates Cholesterol Accumulation in Macrophage Foam Cells.

Abstract

Recent studies have demonstrated that trans-3, 5, 4'-Trimethoxystilbene (TMS), a novel derivative of resveratrol, may suppress the foam cells formation and restrain atherosclerosis in vitro and in vivo. Herein, the molecular mechanisms underlying the protective effects of TMS against atherosclerosis are further delineated. In the present study, the cholesterol-lowering effects of TMS in macrophage-derived foam cell by animal studies, Oil Red O staining, and lipid uptake as well as efflux analysis, are explored. Real-time PCR, western blotting analysis, luciferase reporter assay, electrophoretic mobility shift assay, and immunofluorescent staining are applied for investigating the mechanism involved in atherosclerosis prevention by TMS. Herein, it is revealed that TMS, at a dosage of 10mgkg-1 day-1 , may suppress atherosclerotic plaques within the aorta and arterial intima in apolipoprotein Edeficient mice (ApoE)-/- mice by reducing cholesterol level and macrophages content. Exposure of macrophages to TMS (10µM) can suppress foam cells formation via regulating oxidized low density lipoprotein and cholesterol content in human macrophages through inhibiting scavenger receptors expression and activator protein-1(AP-1) activity. In addition, TMS can activate ERK/Nrf2/HO-1 signaling which increases the expression of ATP-binding cassette transporters. In conclusion, TMS may inhibit the progress of atherosclerosis through regulating cholesterol homeostasis and inhibiting macrophage-derived foam cells formation.