ACE2 expression and activity are enhanced during pregnancy

ACE2 expression and activity are enhanced during pregnancy
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DOI:
10.1152/ajpregu.90592.2008
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发表时间:
2008-12-01
影响因子:
2.8
通讯作者:
Yagil, Chana
Yagil, Chana
中科院分区:
医学3区
文献类型:
--
作者:
Levy, Anat;Yagil, Yoram;Yagil, Chana

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Levy A、Yagil Y、Bursztyn M、Barkalifa R、Scharf S、Yagil C。ACE2 表达和活性在怀孕期间增强。 Am J Physiol Regul Integr Comp Physiol 295:R1953-R1961,2008。首次发表于 2008 年 10 月 22 日; doi:10.1152/ajpregu.90592.2008。 -在当前的研究中,我们研究了正常血压和高血压大鼠妊娠期间ACE2的表达和活性,重点关注子宫和胎盘的相对贡献,肾脏作为参考。我们使用盐敏感性高血压的 Sabra 大鼠模型。我们证实了妊娠晚期存在全身血管舒张状态,血压正常和高血压大鼠的血压均下降。当血压降低时,ACE2在生殖器官中大量表达。妊娠动物中ACE2 mRNA的相对水平为胎盘>肾脏>=子宫,ACE2活性的相对水平为肾脏>胎盘>子宫。在子宫和胎盘中,ACE2 表达不受压力、盐负荷或血压水平的影响。非怀孕大鼠子宫中的 ACE2 活性也不受这些变量的影响,但在怀孕期间,高盐动物的 ACE2 活性有所增加。当估计怀孕期间子宫对 ACE2 mRNA 和活性的总贡献时,我们发现,无论饮食如何,两种品系中 ACE2 mRNA 的量都会增加,但 ACE2 活性仅在高盐动物中增加。我们通过调整器官的质量和数量,进一步估计了妊娠期间子宫、胎盘和肾脏对 ACE2 表达和活性的相对总贡献,发现胎盘是主要贡献者,其次是肾脏和子宫。我们得出的结论是,在怀孕期间,除了肾脏中正常产生的 ACE2 之外,尤其是胎盘,还有子宫,构成了 ACE2 的重要来源,导致总 ACE2 活性估计增加了一倍。这些数据与以下假设一致:妊娠期间短暂的 ACE2 过度表达和活性增加可能对调节子宫胎盘单位的全身和局部血流动力学很重要。
Levy A, Yagil Y, Bursztyn M, Barkalifa R, Scharf S, Yagil C. ACE2 expression and activity are enhanced during pregnancy. Am J Physiol Regul Integr Comp Physiol 295: R1953-R1961, 2008. First published October 22, 2008; doi:10.1152/ajpregu.90592.2008. -In the current study, we investigated the expression and activity of ACE2 during pregnancy in normotensive and hypertensive rats, focusing on the relative contribution of the uterus and the placentas, the kidney serving as a reference. We used the Sabra rat model of salt-sensitive hypertension. We confirmed a systemic vasodilatory state during the third trimester of pregnancy, as evidenced by a reduction in blood pressure, both in normotensive and hypertensive rats. At the time that blood pressure was reduced, ACE2 was expressed abundantly in the reproductive organs. The relative levels of ACE2 mRNA in the pregnant animal were placenta > kidneys >= uterus and of ACE2 activity kidney > placenta > uterus. In the uterus and the placenta, ACE2 expression was unaffected by strain, salt- loading, or the level of blood pressure. ACE2 activity in the uterus of the nonpregnant rat was not affected by any of these variables either, but during pregnancy increased in salt- loaded animals. When estimating the total contribution of the uterus to ACE2 mRNA and activity during pregnancy, we found that the amount of ACE2 mRNA increased in both strains irrespective of diet, but that ACE2 activity increased only in salt-loaded animals. We further estimated the relative total contribution of the uterus, placentas, and kidneys to ACE2 expression and activity during pregnancy by adjusting for mass and number of organs and found that the placentas were the major contributors, followed by the kidney and the uterus. We conclude that during pregnancy, the placentas, in particular, but also the uterus, constitute important sources of ACE2, in addition to its normal production in the kidney, leading to an estimated twofold increase in total ACE2 activity. These data are consistent the hypothesis that transient ACE2 overexpression and increased activity during pregnancy may be important in modulating systemic, as well as local hemodynamics in the uteroplacental unit.