Zysow B R, Kauser K, Lawn R M, Rubanyi G M
Falk Cardiovascular Research Center, Stanford University School of Medicine, Palo Alto, Calif, USA.
Arterioscler Thromb Vasc Biol. 1997 Sep;17(9):1741-5. doi: 10.1161/01.atv.17.9.1741.
Plasma levels of lipoprotein(a) (Lp(a)), are regulated by the synthetic rate of apolipoprotein(a) (apo(a)), a major protein component of this atherogenic lipoprotein. Exogenously administered sex steroid hormones are potent regulators of plasma Lp(a) concentrations. We utilized a recently developed apo(a) yeast artificial chromosome (YAC) transgenic mouse model to study the effects of ovariectomy, estrus cycle, and exogenous administration of ethinyl-estradiol, the partial estrogen receptor agonist, tamoxifen, and progesterone on circulating apo(a) plasma levels. Analysis of liver RNA revealed that estrogen and tamoxifen exerts their plasma apo(a) lowering effect at the level of apo(a) mRNA. This action of estrogen and tamoxifen may contribute to their antiatherosclerotic and cardiovascular protective effect.
脂蛋白(a)[Lp(a)]的血浆水平受载脂蛋白(a)[apo(a)]合成速率的调节，apo(a)是这种致动脉粥样硬化脂蛋白的主要蛋白质成分。外源性给予的性类固醇激素是血浆Lp(a)浓度的有效调节剂。我们利用最近开发的apo(a)酵母人工染色体(YAC)转基因小鼠模型，研究卵巢切除术、发情周期以及外源性给予乙炔雌二醇、部分雌激素受体激动剂他莫昔芬和孕酮对循环中apo(a)血浆水平的影响。肝脏RNA分析显示，雌激素和他莫昔芬在apo(a)mRNA水平发挥降低血浆apo(a)的作用。雌激素和他莫昔芬的这一作用可能有助于它们的抗动脉粥样硬化和心血管保护作用。
