Lee W S, Harder J A, Yoshizumi M, Lee M E, Haber E
Cardiovascular Biology Laboratory, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Nat Med. 1997 Sep;3(9):1005-8. doi: 10.1038/nm0997-1005.
Mortality from atherosclerotic cardiovascular disease is lower in premenopausal women than in age-matched men. It is also lower in postmenopausal women who take estrogens and progestins together rather than estrogens alone. Progesterone receptors were detected in human and rat aortic smooth muscle cells in vivo and in vitro (in subculture). We examined the effect of progesterone on proliferation of smooth muscle cells, important constituents of atherosclerotic plaques. Progesterone at physiologic levels inhibited DNA synthesis and proliferation in these cells in a dose-dependent manner, and pretreatment with the progesterone receptor antagonist RU486 blocked inhibition. Cyclin A and E messenger RNA levels decreased after progesterone treatment but those of cyclin B and D1 did not change. This cell cycle-dependent inhibition of arterial smooth muscle cell proliferation by progesterone may represent a mechanism for the hormone's protective effect against atherosclerosis.
绝经前女性因动脉粥样硬化性心血管疾病导致的死亡率低于年龄匹配的男性。同时服用雌激素和孕激素的绝经后女性的死亡率也低于仅服用雌激素的绝经后女性。在体内和体外（传代培养）的人及大鼠主动脉平滑肌细胞中均检测到了孕激素受体。我们研究了孕激素对平滑肌细胞增殖的影响，平滑肌细胞是动脉粥样硬化斑块的重要组成部分。生理水平的孕激素以剂量依赖的方式抑制这些细胞中的DNA合成和增殖，用孕激素受体拮抗剂RU486预处理可阻断这种抑制作用。孕激素处理后细胞周期蛋白A和E的信使RNA水平下降，但细胞周期蛋白B和D1的信使RNA水平未发生变化。孕激素对动脉平滑肌细胞增殖的这种细胞周期依赖性抑制作用可能是该激素对动脉粥样硬化具有保护作用的一种机制。
