Data_Sheet_3_Angiotensin Converting Enzyme 2 (ACE2) in Pregnancy: Preeclampsia and Small for Gestational Age.PDF

IntroductionAn imbalance in angiotensin (Ang) peptides could contribute to the pathophysiology of preeclampsia (PE) and poor fetal growth.
MethodsWe measured maternal plasma levels of Ang peptides and converting enzymes in non-pregnant women (n = 10), in normal pregnant women (n = 59), women delivering small for gestational age babies (SGA, n = 25) across gestation (13–36 weeks) and in women with PE (n = 14) in their third trimester.
ResultsPlasma ACE, ACE2, and Ang-(1-7) levels, and ACE2 activity were significantly higher in normal pregnant women compared with non-pregnant women; neprilysin (NEP) levels were not changed. In SGA pregnancies, ACE and ACE2 levels were higher in early-mid pregnancy compared with normal pregnant women. In women with PE, plasma ACE, ACE2, NEP, and Ang-(1-7) levels and ACE2 activity were lower than levels in normal pregnant women.
ConclusionThe higher plasma ACE2 levels and activity in pregnancy could be driving the higher Ang-(1-7) levels. The early gestation increases in ACE and ACE2 levels in SGA pregnancies highlights the possibility that these enzymes could be used as potential early biomarkers of poor fetal growth. In women with PE, the reduced ACE2 and NEP levels at term, could be contributing to the reduction in Ang-(1-7) levels. These findings suggest that dysfunctional relationships between two key enzymes in the circulating RAS are involved in the pathogenesis of PE and SGA. Since soluble ACE2 can prevent binding of the novel coronavirus, SARS-CoV-2, to membrane bound ACE2, the interplay between ACE2 and the coronavirus and its impact in pregnancy requires further investigation.

**引言**：血管紧张素（Ang）肽失衡可能参与子痫前期（PE）的病理生理过程及胎儿生长不良的发生。
**方法**：本研究检测了母体血浆中Ang肽及转换酶的水平，研究对象包括：未妊娠女性（n=10）、正常妊娠女性（n=59）、妊娠全程（13~36周）内分娩小于胎龄儿（small for gestational age, SGA，n=25）的妊娠女性，以及妊娠晚期罹患PE的女性（n=14）。
**结果**：与未妊娠女性相比，正常妊娠女性的血浆血管紧张素转换酶（ACE）、血管紧张素转换酶2（ACE2）及Ang-(1-7)水平，以及ACE2活性均显著升高；而脑啡肽酶（neprilysin, NEP）水平无明显变化。在SGA妊娠组中，妊娠早中期的ACE及ACE2水平高于正常妊娠组。罹患PE的女性，其血浆ACE、ACE2、NEP、Ang-(1-7)水平及ACE2活性均低于正常妊娠女性。
**结论**：妊娠时血浆ACE2水平及活性升高可能是Ang-(1-7)水平升高的诱因。SGA妊娠组中，妊娠早期ACE及ACE2水平升高，提示这两种酶可作为胎儿生长不良的潜在早期生物标志物。罹患PE的女性在足月妊娠时，ACE2及NEP水平降低，这可能导致Ang-(1-7)水平下降。本研究结果表明，循环肾素-血管紧张素系统（renin-angiotensin system, RAS）内两种关键酶的功能失调参与了PE及SGA妊娠的发病机制。由于可溶性ACE2可阻止新型冠状病毒（SARS-CoV-2）与膜结合型ACE2的结合，因此ACE2与冠状病毒的相互作用及其对妊娠的影响尚需进一步研究。