The L-NAME mouse model of preeclampsia and impact to long-term maternal cardiovascular health.

The L-NAME mouse model of preeclampsia and impact to long-term maternal cardiovascular health.
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DOI:
10.26508/lsa.202201517
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发表时间:
2022-08-05
影响因子:
4.4
通讯作者:
--
中科院分区:
生物学2区
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--
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先兆子痫的L-NAME小鼠模型模拟了妊娠期疾病的关键方面,但没有证明先兆子痫后个体心血管疾病的长期风险增加。先兆子痫影响全世界20%-8%的妊娠。它与增加长期母体心血管疾病风险有关。本研究评估了血管收缩剂N(ω)-硝基-L-精氨酸甲酯(L-NAME)在小鼠先兆子痫模型中的作用及其对母体心血管健康的长期影响。在这项研究中,我们发现L-NAME的管理模仿先兆子痫的关键特征,包括血压升高,胎儿和胎盘生长受损,并增加循环内皮素-1(血管收缩剂),可溶性fms样酪氨酸激酶-1(抗血管生成因子)和C反应蛋白(炎症标记物)。分娩后,在怀孕期间接受L-NAME的小鼠恢复,与匹配的对照组相比,在分娩后1、2和4周测得的心血管指数没有明显变化。在10周后交付,从L-NAME小鼠收集的动脉收缩显着比对照组更多的苯肾上腺素。此外,这些小鼠的肾脏Mmp 9:Timp 1和心脏Tnf mRNA表达增加,表明炎症增加。这些研究结果表明,尽管在小鼠中给予L-NAME确实模拟了妊娠期间先兆子痫的关键特征,但它似乎没有模拟先兆子痫后个体中心血管疾病风险的不利增加。
The L-NAME mouse model of preeclampsia mimics key aspects of disease in pregnancy, but does not demonstrate the increased long-term risk of cardiovascular disease seen in individuals following preeclampsia. Preeclampsia affects ∼2–8% of pregnancies worldwide. It is associated with increased long-term maternal cardiovascular disease risk. This study assesses the effect of the vasoconstrictor N(ω)-nitro-L-arginine methyl ester (L-NAME) in modelling preeclampsia in mice, and its long-term effects on maternal cardiovascular health. In this study, we found that L-NAME administration mimicked key characteristics of preeclampsia, including elevated blood pressure, impaired fetal and placental growth, and increased circulating endothelin-1 (vasoconstrictor), soluble fms-like tyrosine kinase-1 (anti-angiogenic factor), and C-reactive protein (inflammatory marker). Post-delivery, mice that received L-NAME in pregnancy recovered, with no discernible changes in measured cardiovascular indices at 1-, 2-, and 4-wk post-delivery, compared with matched controls. At 10-wk post-delivery, arteries collected from the L-NAME mice constricted significantly more to phenylephrine than controls. In addition, these mice had increased kidney Mmp9:Timp1 and heart Tnf mRNA expression, indicating increased inflammation. These findings suggest that though administration of L-NAME in mice certainly models key characteristics of preeclampsia during pregnancy, it does not appear to model the adverse increase in cardiovascular disease risk seen in individuals after preeclampsia.
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