Ye Fencheng, Florian Maria, Magder Sheldon A, Hussain Sabah N A
Critical Care and Respiratory Divisions, Royal Victoria Hospital and Meakins-Christie Laboratories, McGill University, Montréal, Québec, Canada.
Steroids. 2002 Mar;67(3-4):305-10. doi: 10.1016/s0039-128x(01)00163-5.
Estrogen promotes endothelial cell proliferation and survival in the vasculture of non-reproductive organs. The main mechanisms through which estrogen exerts its effects on endothelial cells remain unknown. Angiopoietins are newly described modulators of endothelial cell survival and they exert their effects through the activation of endothelial cell-specific Tie-2 receptors. In this study, we evaluated whether estrogen modulates the activity and expression of Tie-2 receptors, Ang-1 and its endogenous antagonist; angiopoietins-2 (Ang-2) in non-reproductive organs. Using RT-PCR, we found that daily administration of 17-beta-estradiol for 8 days in ovariectomized rats results in a significant reduction in tissue Ang-1 mRNA expression. By comparison, estrogen therapy produced a significant increase in Ang-2 mRNA in estrogen-treated rats with heart, kidney and lung Ang-2 mRNA levels reaching 169%, 152% and 224% of those of oil-treated animals, respectively. We also observed that tyrosine phosphorylation of Tie-2 receptors is significantly attenuated in ovariectomized rats treated with 17-beta-estradiol. Our results suggest that the effects of estrogen on the vasculature of non-reproductive organs require the inhibition of angiopoietin-1-Tie-2 receptor pathway and that this inhibition is achieved through simultaneous down-regulation of Ang-1 and Tie-2 expression and elevation in Ang-2 expression.
雌激素可促进非生殖器官血管培养中的内皮细胞增殖和存活。雌激素对内皮细胞发挥作用的主要机制尚不清楚。血管生成素是新发现的内皮细胞存活调节剂，它们通过激活内皮细胞特异性Tie-2受体发挥作用。在本研究中，我们评估了雌激素是否调节非生殖器官中Tie-2受体、血管生成素-1（Ang-1）及其内源性拮抗剂血管生成素-2（Ang-2）的活性和表达。通过逆转录聚合酶链反应（RT-PCR），我们发现，在去卵巢大鼠中连续8天每日给予17-β-雌二醇会导致组织Ang-1 mRNA表达显著降低。相比之下，雌激素治疗使雌激素处理大鼠的Ang-2 mRNA显著增加，心脏、肾脏和肺的Ang-2 mRNA水平分别达到油处理动物的169%、152%和224%。我们还观察到，在用17-β-雌二醇处理的去卵巢大鼠中，Tie-2受体的酪氨酸磷酸化显著减弱。我们的结果表明，雌激素对非生殖器官血管系统的作用需要抑制血管生成素-1-Tie-2受体途径，并且这种抑制是通过同时下调Ang-1和Tie-2的表达以及上调Ang-2的表达来实现的。
