Angiotensinogen T235 expression is elevated in decidual spiral arteries.
Angiotensinogen T235 expression is elevated in decidual spiral arteries.
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蜕膜螺旋动脉中血管紧张素原 T235 表达升高。
DOI：
10.1172/jci119661
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Ward,K
中科院分区：
文献类型：
--
作者：
Morgan,T;Craven,C;Nelson,L;Lalouel,JM;Ward,K
先兆子痫与血管紧张素原（Met 235 Thr）的常见分子变体相关。该变体与血管紧张素原启动子G（-6）A中的突变紧密连锁不平衡，导致体外表达升高。由于血管紧张素II水平可能在与先兆子痫相关的子宫螺旋动脉粥样硬化变化中发挥作用，我们研究了妊娠早期子宫中血管紧张素原的表达。我们使用原位逆转录PCR定位子宫蜕膜中血管紧张素原的转录。然后，我们使用等位基因特异性连接试验和单核苷酸引物延伸试验比较了杂合子妇女的蜕膜T235表达水平和M235水平。在人蜕膜中，血管紧张素原仅在螺旋动脉平滑肌细胞中表达。与M235等位基因相比，杂合子女性T235等位基因的表达显著升高（P < 0.0001）。这些观察结果表明，T235等位基因在蜕膜螺旋动脉的表达升高可能会导致妊娠早期动脉粥样硬化的变化，导致先兆子痫。
Preeclampsia is associated with a common molecular variant of angiotensinogen (Met235Thr). This variant is in tight linkage disequilibrium with a mutation in the angiotensinogen promoter, G(-6)A, which leads to elevated expression in vitro. Since angiotensin II levels could play a role in atherotic changes of the uterine spiral arteries associated with preeclampsia, we investigated angiotensinogen expression in the first trimester uterus. We localized angiotensinogen transcription in uterine decidua using in situ reverse transcription PCR. We then compared decidual T235 expression levels to M235 levels in heterozygous women using an allele-specific ligation assay and a single nucleotide primer extension assay. In human decidua, angiotensinogen is expressed only in spiral artery smooth muscle cells. Heterozygous women have significantly elevated expression of the T235 allele compared to the M235 allele (P < 0.0001). These observations suggest that elevated expression of the T235 allele in decidual spiral arteries may cause first trimester atherotic changes leading to preeclampsia.