Kurokawa Atsuko, Azuma Kosuke, Mita Tomoya, Toyofuku Yukiko, Fujitani Yoshio, Hirose Takahisa, Iwabuchi Kazuhisa, Ogawa Hideoki, Takeda Satoru, Kawamori Ryuzo, Watada Hirotaka
Department of Gynecology, Juntendo University, School of Medicine, Tokyo, Japan.
Endocr J. 2007 Dec;54(6):1027-31. doi: 10.1507/endocrj.k07e-034. Epub 2007 Sep 8.
2-Methoxyestradiol (2-ME) is an endogenous metabolite of estradiol with no affinity for estrogen receptors. It inhibits cell proliferation, thus is a potentially useful drug to block the progression of atherosclerosis. As a first step to examining the anti-atherosclerotic effects of 2-ME, we investigated monocyte adhesion to aortic endothelial cells, which is considered a prerequisite to atherosclerosis in vivo. Eight-week-old Sprague-Dawley rats were ovariectomized then treated by slow-release pellets with placebo, 17-beta-estradiol (5 microg/day), low-dose 2-ME (10 microg/day), or high-dose 2-ME (100 microg/day). After 6 weeks, en face analysis showed an increased number of monocytes adhering to endothelial cells of the thoracic aorta in ovariectomized rats compared with sham-operated controls. This increase was predominantly inhibited by treatment with 17beta-estradiol, and low-dose or high-dose 2-ME. The observed effects were unrelated to changes in serum lipids, blood glucose, or blood pressure. Our data suggested that 2-ME mediates the anti-atherosclerotic actions of estradiol at least in part by preventing monocyte adhesion to the aortic endothelium.
2-甲氧基雌二醇（2-ME）是雌二醇的一种内源性代谢产物，对雌激素受体无亲和力。它能抑制细胞增殖，因此是一种潜在的可用于阻止动脉粥样硬化进展的药物。作为研究2-ME抗动脉粥样硬化作用的第一步，我们研究了单核细胞与主动脉内皮细胞的黏附，这被认为是体内动脉粥样硬化的一个先决条件。将8周龄的Sprague-Dawley大鼠去卵巢，然后用缓释微丸分别给予安慰剂、17-β-雌二醇（5微克/天）、低剂量2-ME（10微克/天）或高剂量2-ME（100微克/天）进行治疗。6周后，整体分析显示，与假手术对照组相比，去卵巢大鼠胸主动脉内皮细胞上黏附的单核细胞数量增加。用17-β-雌二醇、低剂量或高剂量2-ME治疗可显著抑制这种增加。观察到的这些作用与血清脂质、血糖或血压的变化无关。我们的数据表明，2-ME至少部分地通过阻止单核细胞黏附于主动脉内皮来介导雌二醇的抗动脉粥样硬化作用。
