17β-estradiol promotes cholesterol efflux from vascular smooth muscle cells through a liver X receptor α-dependent pathway

摘要: Estrogen has pleiotropic effects on the cardiovascular diseases, yet underlying mechanisms remain incompletely understood. Cholesterol efflux is a key mechanism through which to prevent foam cell formation and development of atherosclerosis. Recent studies highlight role vascular smooth muscle (VSMC)-derived cells in atherogenesis. However, it remains unclear whether estrogen promotes cholesterol from VSMCs inhibits VSMC-derived formation. In present study, we demonstrated that 17β-estradiol (E2) markedly enhanced apolipoprotein (apo)A-1 high-density lipoprotein (HDL) attenuated oxidized low-density (ox-LDL) induced cholesteryl ester accumulation VSMCs, was associated with an increase expression ATP-binding cassette transporters ABCA1 ABCG1. The upregulation ABCG1 by E2 resulted liver X receptor (LXR)α activation, confirmed prevention after inhibition LXRα pharmacological inhibitor or small interfering RNA (siRNA). Furthermore, increased LXRα, via (ER), involvement ERβ use selective ERα antagonists (MPP PHTPP) agonists (PPT DPN). These findings suggest reduces ERβ- LXRα-dependent provide novel insights into anti-atherogenic properties estrogen.