Abstract
High-density lipoprotein (HDL) and 17beta-estradiol independently provide protection against atherosclerosis. Estradiol fatty acyl esters incorporate into HDL and whether this association enhances the atheroprotective properties of HDL is unclear. The study objective was to clarify the role that HDL-associated estradiol fatty acyl esters play in mediating the initial steps of reverse cholesterol transport. Cholesterol efflux potential from cholesterol loaded macrophage cells to HDL-associated estradiol ester or between HDL from premenopausal women and age-matched males and the cellular receptors involved were examined. Human THP-1 macrophages, loaded with [(3)H]cholesterol oleate, acetylated low-density lipoprotein, were pretreated with or without SR-BI inhibitors or an estrogen receptor antagonist and incubated with either HDL-associated estradiol oleate, HDL lacking estradiol oleate, or isolated HDL from females and males, and cholesterol efflux was measured. Cellular internalization and hydrolysis of HDL-associated [(3)H]estradiol ester were determined. HDL-associated estradiol oleate and premenopausal female HDL demonstrated significantly higher cholesterol efflux capacity to media than male HDL. SR-BI and estrogen receptor inhibition significantly reduced this effect. Cells internalized and subsequently hydrolyzed HDL-associated [(3)H]estradiol ester to [(3)H]estradiol and again SR-BI inhibition reduced this internalization. These results demonstrate that HDL-mediated macrophage cholesterol efflux potential is enhanced by HDL-associated estradiol esters.