Zhang E G, Smith S K, Baker P N, Charnock-Jones D S
Department of Obstetrics and Gynaecology, University of Cambridge, The Rosie Hospital, England.
Mol Med. 2001 Sep;7(9):624-35.
Angiopoietin-1 (Ang-1) and its antagonist angiopoietin-2 (Ang-2) act on the endothelial cell Tie-2 receptor to regulate vascular integrity and remodeling. The local balance of these factors and the level of other angiogenic factors determine whether blood vessels grow, are maintained or regress. Profound angiogenesis and vascular remodeling occur in the placenta and this is altered in preeclampsia, a major cause of maternal and fetal morbidity and mortality.
The mRNAs encoding Ang-1, Ang-2, and Tie-2 were detected and localized in human placentae throughout gestation. The mechanism of regulation angiopoietin mRNAs level was determined by explant culture in ambient and reduced oxygen, and in the presence of actinomycin D.
In situ hybridization showed that Ang-2 mRNA was abundant in the syncytiotrophoblast in the first trimester of human pregnancy. Ang-1 mRNA could not be detected by in situ hybridization, but was by reverse transcriptase-polymerase chain reaction (RT-PCR) and Northern blotting. Placental vascular structure is altered in preeclampsia and intrauterine growth restriction, conditions where feto-placental oxygenation is perturbed. In villous explant cultures, a reduction in oxygen tension significantly raised the levels of Ang-2 mRNA, and this was dependent on transcription. However, similar experiments showed that the stability of the Ang-1 message was greatly reduced under these conditions. Thus, hypoxia has opposite effects on Ang-1 and Ang-2 mRNA levels. Placentae obtained from women with preeclampsia had reduced levels of Ang-2 mRNA compared to gestationally matched controls. There was no difference in the levels of Ang-1 mRNAs.
These data show that the relative levels of Ang-1 and Ang-2 mRNA are regulated by local oxygen tension by different mechanisms and that this may be important during normal human placentation.
血管生成素-1（Ang-1）及其拮抗剂血管生成素-2（Ang-2）作用于内皮细胞Tie-2受体，以调节血管完整性和重塑。这些因子的局部平衡以及其他血管生成因子的水平决定了血管是生长、维持还是退化。胎盘会发生深度血管生成和血管重塑，而子痫前期时这种情况会发生改变，子痫前期是母婴发病和死亡的主要原因。
在整个孕期检测并定位编码Ang-1、Ang-2和Tie-2的mRNA在人胎盘中的情况。通过在环境氧和低氧条件下以及存在放线菌素D的情况下进行外植体培养，确定血管生成素mRNA水平的调节机制。
原位杂交显示，在人类妊娠早期，合体滋养层中Ang-2 mRNA丰富。原位杂交无法检测到Ang-1 mRNA，但逆转录聚合酶链反应（RT-PCR）和Northern印迹法可以检测到。子痫前期和宫内生长受限（胎儿-胎盘氧合受到干扰的情况）时胎盘血管结构会发生改变。在绒毛外植体培养中，氧张力降低会显著提高Ang-2 mRNA水平，且这依赖于转录。然而，类似实验表明，在这些条件下Ang-1信息的稳定性大大降低。因此，缺氧对Ang-1和Ang-2 mRNA水平有相反的影响。与孕周匹配的对照组相比，子痫前期妇女的胎盘Ang-2 mRNA水平降低。Ang-1 mRNA水平没有差异。
这些数据表明，Ang-1和Ang-2 mRNA的相对水平通过不同机制受局部氧张力调节，这在正常人类胎盘形成过程中可能很重要。
