Alma L J, De Groot C J M, De Menezes R X, Hermes W, Hordijk P L, Kovačević I
Department of Obstetrics and Gynecology, VU University Medical Center, Amsterdam, The Netherlands; Department of Physiology, VU University Medical Center, Amsterdam, The Netherlands.
Department of Obstetrics and Gynecology, VU University Medical Center, Amsterdam, The Netherlands.
Eur J Obstet Gynecol Reprod Biol. 2018 Jun;225:62-69. doi: 10.1016/j.ejogrb.2018.04.003. Epub 2018 Apr 12.
Hypertensive disorders during pregnancy increase cardiovascular risk later in life by 2 to 9-fold. Endothelial activation is one of the underlying mechanisms of cardiovascular risk. Therefore, we decided to investigate endothelial activation in primiparous women, 2.5 years after a hypertensive pregnancy disorder.
Plasma samples were taken from women 2.5 years after gestational hypertension (GH) or late onset preeclampsia (cases) and from women 2.5 years after a normotensive pregnancy (controls). We studied the effects of patient plasma on the endothelial barrier function of primary human umbilical vein endothelial cells (HUVECs) using Electric Cell-Substrate Impedance Sensing (ECIS) and we measured levels of endothelial activation markers soluble intercellular adhesion molecule 1 (sICAM-1) and soluble endothelial selectin (sE-selectin) in the plasma samples of patients.
Plasma from primiparous women with a history of late onset preeclampsia disrupted the endothelial barrier more than plasma from women with a history of GH. Endothelial resistance was reduced by 22% in samples taken after preeclampsia, 16% after normotensive pregnancy and 3% after GH (p ≤ 0.0001 GH versus preeclampsia and p = 0.0003 versus normotensive pregnancy). We did not find differences in the levels of soluble endothelial activation markers (sICAM-1 p = 0.326 and sE-selectin p = 0.978). However, the BMI ≥25 showed a strong correlation with increased levels of sICAM-1 (p = 0.046) and sE-selectin (p = 0.002).
Our results indicate that GH and late onset preeclampsia are distinct disease entities with a different pathogenic mechanism underlying their cardiovascular risk. Furthermore, this study supports the hypothesis that these two diseases are early manifestations of cardiovascular vulnerability due to an unfavorable risk profile, and that obesity plays a main role. Our results suggest that this high-risk female population would be eligible for preventive care.
孕期高血压疾病会使日后心血管疾病风险增加2至9倍。内皮细胞激活是心血管疾病风险的潜在机制之一。因此，我们决定对初产妇在患妊娠高血压疾病2.5年后的内皮细胞激活情况展开调查。
采集妊娠高血压（GH）或晚发型子痫前期患者产后2.5年的女性（病例组）以及血压正常的孕妇产后2.5年的女性（对照组）的血浆样本。我们采用细胞-基质电阻抗传感技术（ECIS）研究患者血浆对原代人脐静脉内皮细胞（HUVECs）内皮屏障功能的影响，并检测患者血浆样本中内皮细胞激活标志物可溶性细胞间黏附分子1（sICAM-1）和可溶性内皮细胞选择素（sE-选择素）的水平。
有晚发型子痫前期病史的初产妇血浆对内皮屏障的破坏程度高于有GH病史的女性。子痫前期后采集的样本中内皮电阻降低了22%，血压正常的妊娠后降低了16%，GH后降低了3%（GH与子痫前期相比，p≤0.0001；与血压正常的妊娠相比，p = 0.0003）。我们未发现可溶性内皮细胞激活标志物水平存在差异（sICAM-1，p = 0.326；sE-选择素，p = 0.978）。然而，体重指数（BMI）≥25与sICAM-1水平升高（p = 0.046）和sE-选择素水平升高（p = 0.002）密切相关。
我们的结果表明，GH和晚发型子痫前期是不同的疾病实体，其心血管疾病风险背后的致病机制不同。此外，本研究支持以下假设：这两种疾病是由于不良风险状况导致心血管易损性的早期表现，且肥胖起主要作用。我们的结果表明，这一高危女性群体适合接受预防性护理。
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