胆固醇/ALKBH1/ITGA2B在子痫前期胎盘血管血栓形成中的作用。

IF 3.1 2区 生物学 Q2 REPRODUCTIVE BIOLOGY
Yingying Zhang, Eryun Zhang, Ling Li, Yongwei Ren, Jinqiu Zhang, Qiutong Zheng, Minya Sun, Shaojie Zhao, Yugui Cui, Ying Gu, Zhice Xu
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引用次数: 0

摘要

子痫前期(PE)胎盘多发血栓形成风险显著升高,血管内皮通过分泌ITGA2B、vWF和TF在凝血过程中起着至关重要的作用。然而,潜在的病理机制尚不清楚。在本研究中,我们收集了PE和正常妊娠的胎盘血管。与对照组相比,PE样品中ITGA2B蛋白水平上调,表明PE胎盘组织凝血功能增强。此外,PE患者血浆胆固醇水平升高,胎盘血管ALKBH1表达降低,DNA n6 -甲基脱氧腺苷(6ma)水平上调。有趣的是,ITGA2B启动子的DNA 6 mA水平降低。人脐静脉内皮细胞(HUVECs)胆固醇过载实验表明,胆固醇以浓度依赖的方式调节ALKBH1和ITGA2B的蛋白表达。此外,敲除ALKBH1后,ITGA2B蛋白表达增加,但与ALKBH1敲除细胞孵育胆固醇时,未观察到变化。这些发现对胆固醇水平、ALKBH1和ITGA2B在胎盘血管凝血功能中的作用提供了重要的见解。这些信息可能有助于进一步研究PE胎盘血栓形成的潜在治疗靶点和早期预防策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The role of cholesterol/ALKBH1/ITGA2B in thrombosis in the placental vessels of preeclampsia.

The risk of multiple placental thrombosis is significantly elevated in preeclampsia (PE), and the vascular endothelium plays a vital role in coagulation processes through the secretion of ITGA2B, vWF, and TF. However, the underlying pathological mechanisms remain unclear. In this study, placental blood vessels were collected from both PE and normal pregnancies. Protein levels of ITGA2B were found to be up-regulated in PE samples compared to controls, indicating enhanced coagulation function in PE placental tissue. Additionally, Higher cholesterol levels of plasma and lower ALKBH1 expression in placental blood vessels of PE were found, overall DNA N6-methyldeoxyadenosine (6 mA) levels were up-regulated. Interestingly, the DNA 6 mA level at the ITGA2B promoter was decreased. Cholesterol overload experiments in human umbilical vein endothelial cells (HUVECs) demonstrated that cholesterol regulates the protein expression of ALKBH1 and ITGA2B in a concentration-dependent manner. Furthermore, ITGA2B protein expression was increased following ALKBH1 knockout, but no changes were observed when cholesterol was incubated with ALKBH1 knockout cells. These findings provide critical insights into the roles of cholesterol levels, ALKBH1, and ITGA2B in coagulation function within placental blood vessels. This information may contribute to further investigations of potential therapeutic targets and early prevention strategies for placental thrombosis in PE.

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来源期刊
Biology of Reproduction
Biology of Reproduction 生物-生殖生物学
CiteScore
6.30
自引率
5.60%
发文量
214
审稿时长
1 months
期刊介绍: Biology of Reproduction (BOR) is the official journal of the Society for the Study of Reproduction and publishes original research on a broad range of topics in the field of reproductive biology, as well as reviews on topics of current importance or controversy. BOR is consistently one of the most highly cited journals publishing original research in the field of reproductive biology.
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