Hypertension produced by placental ischemia in pregnant rats is associated with increased soluble endoglin expression.
Hypertension produced by placental ischemia in pregnant rats is associated with increased soluble endoglin expression.
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DOI：
10.1161/hypertensionaha.108.123513
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发表时间：
2009-02
期刊：
影响因子：
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通讯作者：
Granger JP
中科院分区：
文献类型：
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作者：
Gilbert JS;Gilbert SA;Arany M;Granger JP
近年来的临床研究表明，血管生成抑制因子如可溶性内皮糖蛋白（sEng）的过量与子痫前期的发生有关。虽然最近的临床研究报告，sEng是增加先兆子痫的妇女，其过度表达的机制仍不清楚。有证据表明，缺氧和血红素氧合酶-1（HO-1）的诱导对sEng表达具有相反的作用，前者刺激，后者抑制。因此，我们假设，胎盘缺血，由于子宫灌注压（RUPP）降低，在怀孕的大鼠会增加sEng的表达，并减少HO-1。通过动脉导管测量平均动脉压（MAP），并通过western blot检测血清和胎盘蛋白。与正常妊娠（NP）对照组相比，RUPP组的MAP升高（132±3对102±2 mm Hg; P<0.001），胎儿（2.35±0.05对1.76±0.08 g; P<0.001）和胎盘重量降低（0.47±0.04对0.58±0.03 g; P<0.01）。RUPP组与NP组相比，血清sEng（0.10±0.02 vs. 0.05±0.01任意像素单位（apu）; P<0.05）和胎盘Eng（4.7±2.3 vs. 1.45±0.42 apu; P<0.05）与胎盘HIF 1-α（1.42±0.25 vs. 0.68 ± 0.09 apu; P < 0.05）表达均沿着增加。与NP母鼠相比，RUPP中胎盘HO-1（1.4±0.3 vs.2.5 ±0.1 apu; P<0.05）表达降低。目前的研究结果支持我们的假设，即胎盘缺血，由于RUPP增加的表达sEng和转移的平衡，在母体循环血管生成因子对血管生成抑制状态。本研究提供了进一步的证据，胎盘缺血是一个强大的在体内刺激血管生成抑制因子在怀孕期间。
Recent clinical studies indicate an excess of angiostatic factors such as soluble endoglin (sEng) is related to the occurrence of preeclampsia. Although recent clinical studies report that sEng is increased in preeclamptic women, the mechanisms underlying its over-expression remain unclear. Evidence suggests that hypoxia and induction of heme oxygenase-1 (HO-1) have opposing effects on sEng expression, the former stimulatory and the latter inhibitory. Hence, we hypothesized that placental ischemia due to reduced uterine perfusion pressure (RUPP) in the pregnant rat would increase sEng expression, and decrease HO-1. Mean arterial pressure (MAP) was obtained via arterial catheter and serum and placental proteins were measured by western blot. MAP was increased (132±3 vs. 102±2 mm Hg; P<0.001) and fetal (2.35±0.05 vs. 1.76±0.08 g; P<0.001) and placental weight were decreased (0.47±0.04 vs. 0.58±0.03 g; P<0.01) in the RUPP compared to normal pregnant (NP) controls. Serum sEng (0.10±0.02 vs. 0.05±0.01 arbitrary pixel units (apu); P<0.05) and placental Eng (4.7±2.3 vs. 1.45±0.42 apu; P<0.05) were increased along with placental HIF1-α (1.42±0.25 vs. 0.68 ± 0.09 apu; P < 0.05) expression in the RUPP vs. the NP dams. Placental HO-1 (1.4±0.3 vs. 2.5±0.1 apu; P<0.05) expression decreased in the RUPP compared to NP dams. The present findings support our hypothesis that placental ischemia due to RUPP increases the expression of sEng and shifts the balance of angiogenic factors in the maternal circulation towards an angiostatic state. The present study provides further evidence that placental ischemia is a strong in vivo stimulus of angiostatic factors during pregnancy.