ArticlePlacenta2016
High levels of HtrA4 observed in preeclamptic circulation drastically alter endothelial gene expression and induce inflammation in human umbilical vein endothelial cells.
Article in Placenta, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Circulating endocan and preeclampsia: a meta-analysis.Bioscience reports · 2020Pooled it
- Pregnancy-related disorders: molecular mechanisms and management.Molecular biomedicine · 2026Review
- New Frontiers in the Pathophysiology of Hypertensive Pregnancy Disorders: A Systematic Review of Molecular Insights into Preeclampsia.Current issues in molecular biology · 2026Review
- Understanding the involvement of HtrA4 during syncytiotrophoblast differentiation.Frontiers in cell and developmental biology · 2026Article
- Htra4 promotes vascular endothelial cell injury and is associated with the early-onset of preeclampsia.Scientific reports · 2025Article
- Culture of cryopreserved first trimester placental tissues to study syncytial renewal.Scientific reports · 2025Article
- Identification and validation of feature genes associated with M1 macrophages in preeclampsia.Aging · 2023Article
- Article
- The first-trimester serum high-temperature requirement protease A4 and uterine artery Doppler for the prediction of preeclampsia.Scientific reports · 2023Article
- Sex-specific effects of maternal weight loss on offspring cardiometabolic outcomes in the obese preeclamptic-like mouse model, BPH/5.Physiological reports · 2022Article
- Overview of Human HtrA Family Proteases and Their Distinctive Physiological Roles and Unique Involvement in Diseases, Especially Cancer and Pregnancy Complications.International journal of molecular sciences · 2021Review
- HtrA4 is up-regulated during trophoblast syncytialization and BeWo cells fail to syncytialize without HtrA4.Scientific reports · 2021Article
- HtrA4 may play a major role in inhibiting endothelial repair in pregnancy complication preeclampsia.Scientific reports · 2019Article
- Maternal HtrA3 optimizes placental development to influence offspring birth weight and subsequent white fat gain in adulthood.Scientific reports · 2017Article
- Effect of Reduced INR in Early Pregnancy on the Occurrence of Preeclampsia: A Retrospective Cohort Study.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisArticle
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionPreeclampsia (PE) is a life-threatening pregnancy disorder characterized by wide-spread endothelial dysfunction. Placental factors circulating in the maternal blood are believed to cause endothelial dysfunction. Our previous study identified HtrA4 as a placenta-specific serine protease that is released into the maternal circulation and significantly increased in early-onset PE. In this study, we examined the impact of HtrA4 on expression of endothelial genes related to vessel biology, using human umbilical vein endothelial cells (HUVECs) as a model.
methodsHUVECs were treated with 0 or 3 μg/ml HtrA4 (highest concentration seen in PE circulation) for 24 h and analysed by an endothelial cell biology PCR array containing 84 genes. HtrA4-induced changes were then validated by real-time RT-PCR and ELISA for time and dose dependency.
resultsHigh levels of HtrA4 significantly altered the expression of a range of genes related to inflammation, vaso-activity, angiogenesis, cell adhesion, platelet activation and coagulation. In particular, pro-inflammatory genes IL6, PTGS2 (COX2) and IL1B were significantly increased by HtrA4. IL6 protein in HUVEC media was also drastically increased. THBD, an anticoagulant factor reported to be increased in PE, was significantly up-regulated by HtrA4. In contrast, THBS1, which is involved in many regulatory processes of endothelial cell biology, was severely down-regulated by HtrA4. DISCUSSION: HtrA4 significantly increased the inflammatory responses of HUVECs, and altered their expression of a number of genes important for vessel biology. These data suggest that placenta-derived HtrA4 that is increased in PE circulation is a potential causal factor of endothelial dysfunction.
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