Human macrophage cholesterol efflux potential is enhanced by HDL-associated 17β-estradiol fatty acyl esters
Human macrophage cholesterol efflux potential is enhanced by HDL-associated 17β-estradiol fatty acyl esters
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DOI：
10.1016/j.jsbmb.2009.04.008
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发表时间：
2009-08-01
影响因子：
4.1
通讯作者：
Jauhiainen, Matti
中科院分区：
文献类型：
--
作者：
Badeau, Robert M.;Metso, Jari;Jauhiainen, Matti
高密度脂蛋白（HDL）和17 β-雌二醇独立地提供对动脉粥样硬化的保护。雌二醇脂肪酸酯与HDL结合，这种结合是否增强HDL的抗动脉粥样硬化特性尚不清楚。研究目的是阐明HDL相关的雌二醇脂肪酰酯在介导胆固醇逆向转运的初始步骤中的作用。从胆固醇负载的巨噬细胞的胆固醇流出的潜力HDL相关的雌二醇酯或之间的HDL绝经前妇女和年龄匹配的男性和细胞受体的参与进行了检查。人THP-1巨噬细胞，负载[H-3]胆固醇油酸酯，乙酰化低密度脂蛋白，预处理或不与SR-BI抑制剂或雌激素受体拮抗剂，并与HDL相关的雌二醇油酸酯，HDL缺乏雌二醇油酸酯，或从女性和男性分离的HDL孵育，并测量胆固醇流出。测定HDL相关的[H-3]雌二醇酯的细胞内化和水解。HDL相关的油酸雌二醇和绝经前女性HDL表现出显着较高的胆固醇流出能力的媒体比男性HDL SR-BI和雌激素受体抑制剂显着降低这种影响。细胞内化并随后将HDL相关的[H-3]雌二醇酯水解为[H-3]雌二醇，SR-BI抑制再次降低了这种内化。这些结果表明，HDL介导的巨噬细胞胆固醇流出的潜力是由HDL相关的雌二醇酯增强。(C)2009爱思唯尔有限公司版权所有。
High-density lipoprotein (HDL) and 17 beta-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 [H-3]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 [H-3]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 [H-3]estradiol ester to [H-3]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. (C) 2009 Elsevier Ltd. All rights reserved.