Badeau Robert M, Metso Jari, Wähälä Kristiina, Tikkanen Matti J, Jauhiainen Matti
National Institute of Health and Welfare and FIMM, Institute for Molecular Medicine, PO Box 104, 00251 Helsinki, Finland.
J Steroid Biochem Mol Biol. 2009 Aug;116(1-2):44-9. doi: 10.1016/j.jsbmb.2009.04.008. Epub 2009 May 3.
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.
高密度脂蛋白（HDL）和17β-雌二醇可独立提供抗动脉粥样硬化保护作用。雌二醇脂肪酰酯可掺入HDL中，而这种关联是否会增强HDL的抗动脉粥样硬化特性尚不清楚。本研究的目的是阐明与HDL相关的雌二醇脂肪酰酯在介导胆固醇逆向转运初始步骤中所起的作用。研究检测了胆固醇负载的巨噬细胞向与HDL相关的雌二醇酯的胆固醇流出潜力，以及绝经前女性和年龄匹配男性的HDL之间的胆固醇流出潜力，并检测了其中涉及的细胞受体。用人THP-1巨噬细胞，负载[（3）H]胆固醇油酸酯、乙酰化低密度脂蛋白，用或不用SR-BI抑制剂或雌激素受体拮抗剂预处理，然后与与HDL相关的雌二醇油酸酯、缺乏雌二醇油酸酯的HDL或来自女性和男性的分离HDL一起孵育，并测量胆固醇流出。测定了与HDL相关的[（3）H]雌二醇酯的细胞内化和水解情况。与HDL相关的雌二醇油酸酯和绝经前女性的HDL对培养基的胆固醇流出能力明显高于男性HDL。SR-BI和雌激素受体抑制显著降低了这种作用。细胞内化并随后将与HDL相关的[（3）H]雌二醇酯水解为[（3）H]雌二醇，同样，SR-BI抑制降低了这种内化。这些结果表明，与HDL相关的雌二醇酯可增强HDL介导的巨噬细胞胆固醇流出潜力。
