Soluble flt-1 and the angiopoietins in the development and regulation of placental vasculature
Soluble flt-1 and the angiopoietins in the development and regulation of placental vasculature
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DOI：
10.1046/j.1469-7580.2002.00063.x
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发表时间：
2002-06-01
影响因子：
2.4
通讯作者：
Charnock-Jones, DS
中科院分区：
文献类型：
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作者：
Charnock-Jones, DS
胎盘的关键作用之一是调节母体和胎儿循环之间的氧气、营养物质和废物的交换。虽然一些营养物质被主动吸收，但氧气是被动运输的（即它沿着简单的浓度梯度移动）。为了确保妊娠过程中有足够的供应，人类胎盘中的血管结构重塑以促进这种转移。在氧气有限的条件下，例如在高海拔地区，这些适应变得更加明显。在胎盘从高海拔地区获得的血管的平均直径增加，血管周围细胞（周细胞）的数量减少。周细胞在调节内皮细胞功能中起重要作用，并且在它们不存在的情况下，内皮细胞对生长因子撤回敏感。正常妊娠中发生的血管重塑部分由可溶性因子介导（一些由周细胞产生），这些因子的水平反过来又可由局部氧张力调节。我们已经证明，编码这两种血管生成素的mRNA都存在于胎盘中，并且都受到局部pO（2）的调节。Ang-2 mRNA的转录在低氧条件下增加，Ang-1 mRNA的稳定性在类似条件下降低。因此，在胎盘中，编码这些拮抗因子的mRNA的比例随着pO（2）的降低而改变（有利于Ang-2）。在胎盘中看到的适应性变化及其实现机制可能是普遍适用的。
One of the key roles of the placenta is to mediate exchange of oxygen, nutrients and waste products between the maternal and fetal circulations. While some nutrients are actively taken up, oxygen is passively transported (i.e. it moves down a simple concentration gradient). To ensure an adequate supply as gestation progresses, the vascular structures in the human placenta remodel to facilitate this transfer. Under conditions in which oxygen is limited, at high altitude for example, these adaptations become more pronounced. In placentae obtained from high altitude the mean diameter of vessels is increased and the number of perivascular cells (pericytes) is reduced. Pericytes play an important role in modulating endothelial cell function and in their absence the endothelial cells are sensitive to growth factor withdrawal. The vascular remodelling that occurs in normal pregnancy is in part mediated by soluble factors (some produced by pericytes) and the level of these may in turn be regulated by local oxygen tension. We have shown that the mRNAs encoding both angiopoietins are present in the placenta and both are regulated by local pO(2). Ang-2 mRNA transcription is increased under reduced oxygen and the stability of Ang-1 mRNA is reduced under similar conditions. Thus the ratio of mRNAs encoding these antagonistic factors changes (in favour of Ang-2), in the placenta in response to a reduction in pO(2). The adaptations seen in the placenta and the mechanism by which they are achieved may be generally applicable.