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MicroRNA targeting VEGF are related to vascular dysfunction in preeclampsia.
Bioscience Reports ( IF 3.8 ) Pub Date : 2021-07-28 , DOI: 10.1042/bsr20210874
Isabel Witvrouwen 1, 2 , Dominique Mannaerts 3, 4 , Jessica Ratajczak 1 , Evi Boeren 1 , Ellen Faes 3, 4 , Amaryllis H Van Craenenbroeck 5, 6 , Yves Jacquemyn 3, 4 , Emeline M Van Craenenbroeck 1, 2
Affiliation  

In preeclampsia (PE) pre-existent maternal endothelial dysfunction leads to impaired placentation and vascular maladaptation. The vascular endothelial growth factor (VEGF) pathway is essential in the placentation process and VEGF expression is regulated through post-transcriptional modification by microRNAs. We investigated the expression of VEGF related circulating miR-16, miR-29b, miR-126, miR-155 and miR-200c in PE versus healthy pregnancies (HP), and their relation with vascular function, oxidative stress and systemic inflammation.In this case-control study, 24 women with early PE (in vivo vascular function (flow mediated dilation (FMD), modified FMD (mFMD), carotid-femoral pulse wave velocity (CF-PWV), augmentation index (AIx75) and reactive hyperaemia index (RHI)). FMD, CF-PWV, AIx75 and RHI were all significantly impaired in PE (p<0.05). PE patients had reduced levels of miR-16 (5.53±0.36vs5.84±0.61) and increased levels of miR-200c (1.34±0.57vs0.97±0.68) (p<0.05). Independent of age and parity, miR-16 was related to impaired FMD (ß 2.771, 95% C.I. 0.023-5.519, p=0.048) and mFMD (ß3.401, 95% C.I. 0.201-6.602, p=0.038). Likewise, miR-200c was independently associated with CF-PWV (ß0.513, 95% C.I. 0.034-0.992, p=0.036). In conclusion, circulating levels of miR-16 were lower in PE, which correlated with impaired endothelial function. Circulating miR-200c was increased in PE and correlated with higher arterial stiffness. These findings suggest a post-transcriptional dysregulation of the VEGF pathway in PE and identify miR-16 and miR-200c as possible diagnostic biomarkers for PE.

中文翻译:

靶向 VEGF 的 MicroRNA 与先兆子痫的血管功能障碍有关。

在先兆子痫 (PE) 中,预先存在的母体内皮功能障碍导致胎盘形成受损和血管适应不良。血管内皮生长因子 (VEGF) 通路在胎盘形成过程中是必不可少的,并且 VEGF 的表达通过 microRNA 的转录后修饰来调节。我们研究了 VEGF 相关循环 miR-16、miR-29b、miR-126、miR-155 和 miR-200c 在 PE 与健康妊娠 (HP) 中的表达,以及它们与血管功能、氧化应激和全身炎症的关系。这项病例对照研究,24 名患有早期 PE(体内血管功能(血流介导扩张 (FMD)、改良 FMD (mFMD)、颈股动脉脉搏波速度 (CF-PWV)、增强指数 (AIx75) 和反应性充血)的女性指数 (RHI)). FMD、CF-PWV、AIx75 和 RHI 在 PE 中均显着受损 (p<0.05)。PE患者的miR-16水平降低(5.53±0.36vs5.84±0.61),miR-200c水平升高(1.34±0.57vs0.97±0.68)(p<0.05)。与年龄和胎次无关,miR-16 与受损的 FMD (ß 2.771, 95% CI 0.023-5.519, p=0.048) 和 mFMD (ß3.401, 95% CI 0.201-6.602, p=0.038) 有关。同样,miR-200c 与 CF-PWV 独立相关 (ß0.513, 95% CI 0.034-0.992, p=0.036)。总之,miR-16 的循环水平在 PE 中较低,这与内皮功能受损有关。循环 miR-200c 在 PE 中增加并与更高的动脉僵硬度相关。这些发现表明 PE 中 VEGF 通路的转录后失调,并将 miR-16 和 miR-200c 确定为 PE 的可能诊断生物标志物。57vs0.97±0.68) (p<0.05)。与年龄和胎次无关,miR-16 与受损的 FMD (ß 2.771, 95% CI 0.023-5.519, p=0.048) 和 mFMD (ß3.401, 95% CI 0.201-6.602, p=0.038) 有关。同样,miR-200c 与 CF-PWV 独立相关 (ß0.513, 95% CI 0.034-0.992, p=0.036)。总之,miR-16 的循环水平在 PE 中较低,这与内皮功能受损有关。循环 miR-200c 在 PE 中增加并与更高的动脉僵硬度相关。这些发现表明 PE 中 VEGF 通路的转录后失调,并将 miR-16 和 miR-200c 确定为 PE 的可能诊断生物标志物。57vs0.97±0.68) (p<0.05)。与年龄和胎次无关,miR-16 与受损的 FMD (ß 2.771, 95% CI 0.023-5.519, p=0.048) 和 mFMD (ß3.401, 95% CI 0.201-6.602, p=0.038) 有关。同样,miR-200c 与 CF-PWV 独立相关 (ß0.513, 95% CI 0.034-0.992, p=0.036)。总之,miR-16 的循环水平在 PE 中较低,这与内皮功能受损有关。循环 miR-200c 在 PE 中增加并与更高的动脉僵硬度相关。这些发现表明 PE 中 VEGF 通路的转录后失调,并将 miR-16 和 miR-200c 确定为 PE 的可能诊断生物标志物。miR-200c 与 CF-PWV 独立相关 (ß0.513, 95% CI 0.034-0.992, p=0.036)。总之,miR-16 的循环水平在 PE 中较低,这与内皮功能受损有关。循环 miR-200c 在 PE 中增加并与更高的动脉僵硬度相关。这些发现表明 PE 中 VEGF 通路的转录后失调,并将 miR-16 和 miR-200c 确定为 PE 的可能诊断生物标志物。miR-200c 与 CF-PWV 独立相关 (ß0.513, 95% CI 0.034-0.992, p=0.036)。总之,miR-16 的循环水平在 PE 中较低,这与内皮功能受损有关。循环 miR-200c 在 PE 中增加并与更高的动脉僵硬度相关。这些发现表明 PE 中 VEGF 通路的转录后失调,并将 miR-16 和 miR-200c 确定为 PE 的可能诊断生物标志物。
更新日期:2021-07-28
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