Maternal systemic vascular dysfunction in a primate model of defective uterine spiral artery remodeling
Maternal systemic vascular dysfunction in a primate model of defective uterine spiral artery remodeling
复制标题
灵长类动物子宫螺旋动脉重构缺陷模型的母体全身血管功能障碍
DOI：
10.1152/ajpheart.00613.2020
复制
发表时间：
2021-04-01
影响因子：
4.8
通讯作者：
Pepe, Gerald J.
中科院分区：
文献类型：
--
作者：
Albrecht, Eugene D.;Babischkin, Jeffery S.;Pepe, Gerald J.
子宫螺旋动脉重构（UAR）对胎盘灌注和胎儿发育至关重要。UAR的缺陷是胎盘缺血性疾病的基础，例如，先兆子痫，其导致母体全身血管内皮功能障碍和高血压。我们已经建立了一个模型，受损的UAR过早地提高母体血清雌二醇水平在头三个月的狒狒怀孕。然而，目前尚不清楚这种实验范式是否与母体血管内皮功能障碍有关。因此，在本研究中，狒狒在妊娠第25-59天接受雌二醇给药，以抑制UAR和在第165天（期限= 184天）外周和骨骼肌中测定的母体血管功能，骨骼肌占体重的40%以上，占静息全身血管阻力的25%。在UAR抑制狒狒中，母体血清sFlt-1水平高2.5倍（P < 0.05），骨骼肌小动脉内皮一氧化氮合酶（eNOS）蛋白表达和管腔面积以及骨骼肌毛细血管密度低30-50%（P < 0.05）。与eNOS表达、管腔面积和毛细血管密度的这些变化一致，UAR缺陷狒狒的母体肱动脉血流介导的扩张和容积流量分别降低70%和55%（P < 0.05），平均动脉血压升高29%（P < 0.01）。总之，在UAR受损的狒狒模型中，母体血管功能被破坏。这些结果突出了这种灵长类动物模型的翻译影响和相关性的不良条件下的人类妊娠不正确的子宫动脉transformation.NEW和值得注意的孕产妇血管功能障碍是异常人类妊娠的标志，特别是早发性先兆子痫，引起受损的UAR。本研究提出了新的发现，母体全身血管功能障碍是在狒狒实验模型受损的UAR。这项研究强调了这种非人灵长类动物模型与人类妊娠不良条件的翻译相关性，这些不良条件是由UAR缺陷所支撑的。
Uterine spiral artery remodeling (UAR) is essential for placental perfusion and fetal development. A defect in UAR underpins placental ischemia disorders, e.g., preeclampsia, that result in maternal systemic vascular endothelial dysfunction and hypertension. We have established a model of impaired UAR by prematurely elevating maternal serum estradiol levels during the first trimester of baboon pregnancy. However, it is unknown whether this experimental paradigm is associated with maternal vascular endothelial dysfunction. Therefore, in the present study baboons were administered estradiol on days 25-59 of gestation to suppress UAR and maternal vascular function determined on day 165 (term = 184days) peripherally and in skeletal muscle, which accounts for over 40% of body mass and 25% of resting systemic vascular resistance. Maternal serum sFlt-1 levels were 2.5-fold higher (P < 0.05), and skeletal muscle arteriolar endothelial nitric oxide synthase (eNOS) protein expression and luminal area, and skeletal muscle capillary density were 30-50% lower (P < 0.05) in UAR suppressed baboons. Coinciding with these changes in eNOS expression, luminal area, and capillary density, maternal brachial artery flow-mediated dilation and volume flow were 70% and 55% lower (P < 0.05), respectively, and mean arterial blood pressure 29% higher (P < 0.01) in UAR defective baboons. In summary, maternal vascular function was disrupted in a baboon model of impaired UAR. These results highlight the translational impact of this primate model and relevance to adverse conditions of human pregnancy underpinned by improper uterine artery transformation.NEW & NOTEWORTHY Maternal vascular dysfunction is a hallmark of abnormal human pregnancy, particularly early-onset preeclampsia, elicited by impaired UAR. The present study makes the novel discovery that maternal systemic vascular dysfunction was induced in a baboon experimental model of impaired UAR. This study highlights the translational relevance of this nonhuman primate model to adverse conditions of human pregnancy underpinned by defective UAR.