Effects of short-term hormone replacement therapies on low-density lipoprotein metabolism in cynomologus monkeys.
Effects of short-term hormone replacement therapies on low-density lipoprotein metabolism in cynomologus monkeys.
复制标题
短期激素替代疗法对食蟹猴低密度脂蛋白代谢的影响。
DOI：
10.1161/01.atv.17.6.1128
复制
发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Adams,MR
中科院分区：
文献类型：
--
作者：
Wagner,JD;Schwenke,DC;Zhang,L;Applebaum-Bowden,D;Bagdade,JD;Adams,MR
雌激素替代疗法可降低女性患冠心病的风险，并降低猴子动脉粥样硬化的程度。在我们以前的研究中，雌激素治疗降低了动脉LDL的降解和积累，从而表明雌激素抑制动脉粥样硬化进展的一种机制。孕激素对这些过程的影响尚不清楚。本研究的目的是确定口服雌激素（结合马雌激素）和孕酮（醋酸甲羟孕酮）单独或联合对动脉粥样硬化刺激12周后动脉LDL代谢的影响。选择这一相对较短的治疗时间，以确定在大量内皮下巨噬细胞蓄积之前对动脉LDL代谢的影响。与之前的研究（治疗16至18周）相反，当内膜中存在巨噬细胞时，雌激素和巨噬细胞蛋白（或其组合）对动脉LDL代谢的任何指数都没有任何影响。这些结果表明，雌激素可能优先降低LDL代谢的巨噬细胞对正常动脉细胞的影响很小。与动脉LDL代谢相反，在用雌激素或雌激素加雷公藤红素治疗的动物中，肝脏LDL摄取显著增加。尽管增加了肝脏的LDL摄取，但与对照组和孕激素治疗组相比，雌激素和雌激素加孕酮治疗组的肝脏脂质含量均显著降低了1.50%。肝脏胆固醇含量的降低被假设是由于胆固醇的胆汁分泌增加。
Estrogen replacement therapy reduces the risk of coronary heart disease in women and decreases the extent of atherosclerosis in monkeys. In our previous studies, estrogen treatment decreased arterial LDL degradation and accumulation, thus indicating one mechanism by which estrogen inhibits the progression of atherosclerosis. The influence of progestins on these processes remains unclear. The objective of this study was to determine the effects of oral estrogen (conjugated equine estrogens) and progestin (medroxyprogesterone acetate) alone or in combination on arterial LDL metabolism after 12 weeks of atherogenic stimulus. This relatively short period of treatment was chosen to determine effects on arterial LDL metabolism before substantial subendothelial macrophage accumulation. In contrast to previous studies (16 to 18 weeks of treatment), when macrophages were present in the intima, neither estrogen nor progestin (nor their combination) had any effect on any index of arterial LDL metabolism. These results suggest that estrogen may preferentially reduce LDL metabolism in macrophages with little effect on cells of the normal artery. In contrast to arterial LDL metabolism, hepatic LDL uptake was significantly increased in animals treated with estrogen or estrogen plus progestin. Despite the increased LDL uptake by the liver, hepatic lipid content was significantly decreased by ≈50% in both estrogen and estrogen-plus-progestin treatment compared with control and progestin-treated animals. The decrease in hepatic cholesterol content is hypothesized to be due to increased biliary secretion of cholesterol.