{"title":"The role of cholesterol/ALKBH1/ITGA2B in thrombosis in the placental vessels of preeclampsia.","authors":"Yingying Zhang, Eryun Zhang, Ling Li, Yongwei Ren, Jinqiu Zhang, Qiutong Zheng, Minya Sun, Shaojie Zhao, Yugui Cui, Ying Gu, Zhice Xu","doi":"10.1093/biolre/ioaf067","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biology of Reproduction","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1093/biolre/ioaf067","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"REPRODUCTIVE BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
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.