Anti-atherogenic effects of resveratrol via liver X receptor alpha-dependent upregulation of ATP-binding cassette transporters A1 and G1 in macrophages

作者：Chang Chun Yu; Lee Tsung Han^*; Sheu Wayne H H

来源：Journal of Functional Foods, 2012, 4(4): 727-735.

DOI：10.1016/j.jff.2012.04.012

• Resveratrol
• Foam cell
• Atherosclerosis
• LXR alpha
• ATP-binding cassette transporter
• Scavenger receptor

Resveratrol (RSV), a phenolic component, is found in grape skins, peanuts, pistachios and red wine. RSV has protective activities in atherosclerosis, yet the detailed mechanisms are not fully elucidated. In the present study, we observed that RSV inhibited oxLDL-mediated lipid accumulation through the enhancement of cholesterol efflux in THP-1-derived macrophages and explored the possible underlying mechanisms. RSV dose-dependently enhanced the mRNA and protein levels of ATP-binding membrane cassette transporters A1 and G1 (ABCA1 and ABCG1) but had no effect on the mRNA expression of scavenger receptor class BI (SR-BI) in cholesterol homeostasis. Additionally, the functional inhibition of ABCA1 and ABCG1 with short hairpin RNA abrogated the effects of RSV on lipid accumulation. The upregulation of ABCA1 and ABCG1 by RSV depended on LXR alpha, as evidenced by an increase in the nuclear levels of LXRa through the induction of nuclear translocation. The functional inhibition of LXR alpha with a pharmacological inhibitor, geranylgeranyl pyrophosphate (GGPP), abolished the RSV-mediated protective effects in macrophages. These findings suggest that LXR alpha-dependent upregulation of ABCA1 and ABCG1 might mediate the beneficial effects of RSV, which ameliorated the oxLDL-mediated lipid accumulation in the process of lipid-laden foam cells formation.

• 单位
  中国医科大学