Turku PET Centre, Turku University Central Hospital, Turku, Finland.
Eur J Clin Invest. 2013 Apr;43(4):317-23. doi: 10.1111/eci.12044. Epub 2013 Feb 9.
Premenopausal women have a lower incidence of cardiovascular disease compared to men of the same age. Endogenous oestrogens, especially estradiol, presumably protect against atherosclerosis by a variety of mechanisms. Reverse cholesterol transport (RCT) mechanisms also provide protection against this disease. RCT is defined as the removal of cholesterol from peripheral macrophage foam cells, via high-density lipoproteins (HDL), and cholesterol transportation to the liver for excretion. We have previously shown in a preliminary study that HDL, isolated from premenopausal women, enhanced macrophage cholesterol efflux compared to HDL derived from age-matched male subjects.
Here, we expanded this study by analysing a larger population of healthy volunteers and evaluated the capacity of HDL derived from women with high or low serum E2 concentrations, mainly representing premenopausal and postmenopausal women, respectively, or men (each group consisting of 30 subjects) to facilitate cholesterol removal from human THP-1 macrophages. HDL isolated from serum samples was incubated with [(3)H] cholesterol oleate-loaded macrophages for 16 h, after which cholesterol efflux to HDL was determined.
No significant differences in the efflux-promoting ability of HDL existed among the three groups. Relevant plasma factors involved in further steps of RCT, such as cholesterol ester transfer protein (CETP), phospholipid transfer protein (PLTP) and lecithin:cholesterol acyltransferase (LCAT) activities were also analysed, but no differences were observed among the study groups.
The results do not support a role for estradiol status or gender in modifying the initial step of RCT as a protective mechanism against cardiovascular disease.
与同年龄的男性相比，绝经前女性患心血管疾病的发病率较低。内源性雌激素，尤其是雌二醇，可能通过多种机制预防动脉粥样硬化。胆固醇逆转运（RCT）机制也为预防这种疾病提供了保护。RCT 的定义是通过高密度脂蛋白（HDL）从外周巨噬细胞泡沫细胞中去除胆固醇，并将胆固醇转运到肝脏进行排泄。我们之前的初步研究表明，与来自年龄匹配的男性受试者的 HDL 相比，从绝经前女性中分离出的 HDL 增强了巨噬细胞胆固醇流出。
在这里，我们通过分析更大的健康志愿者群体扩展了这项研究，并评估了 HDL 的能力，这些 HDL 来自血清 E2 浓度高或低的女性，主要代表绝经前和绝经后女性，或男性（每组 30 名受试者），以促进人 THP-1 巨噬细胞中胆固醇的去除。将从血清样本中分离出的 HDL 与 [(3)H] 胆固醇油酸负载的巨噬细胞孵育 16 小时后，测定胆固醇向 HDL 的流出。
三组之间 HDL 促进流出的能力没有显著差异。还分析了涉及 RCT 进一步步骤的相关血浆因子，如胆固醇酯转移蛋白（CETP）、磷脂转移蛋白（PLTP）和卵磷脂：胆固醇酰基转移酶（LCAT）活性，但研究组之间没有观察到差异。
这些结果不支持雌二醇状态或性别在修饰 RCT 的初始步骤中发挥作用，作为预防心血管疾病的保护机制。
