Hyperadhesive von Willebrand Factor Contributes to Pathogenesis of Preeclampsia

Authors

• Yajuan Wang
• Chenyu Wang
• Katie L Houck
• Xiaoli Gao
• Yuanyuan Chen
• Xin Xu
• Xue Zhao
• Miguel A Cruz
• Shu Zhang
• Chester Q Li
• Fengxia Xue
• Min Li
• Swati Shree
• Jing-Fei Dong
• Cha Han

Language

English

Publication Date

8-1-2026

Journal

Arteriosclerosis, Thrombosis, and Vascular Biology

DOI

10.1161/ATVBAHA.125.324258

PMID

42273730

PMCID

PMC13384387

PubMedCentral® Posted Date

6-11-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Background: Preeclampsia is the most common complication of pregnancy, significantly affecting maternal and fetal health, and is characterized by placental and systemic endotheliopathy. Patients with preeclampsia have elevated levels of VWF (von Willebrand Factor), which is associated with poor clinical outcomes. However, whether VWF serves as a marker for endotheliopathy or contributes to the pathogenesis of preeclampsia remains poorly understood.

Methods: We investigated the role of hyperadhesive VWF in the development of preeclampsia by studying patients, evaluating mouse models, and performing in vitro experiments.

Results: We show that patients develop VWF- and fibrin-rich thrombosis in the placenta and have significantly elevated levels of VWF adhesive activity and placenta-derived extracellular vesicles. In mouse models, pregnant wild-type mice infused with hyperadhesive VWF alone, or in combination with placenta-derived extracellular vesicles, developed a preeclampsia-like condition, which was reduced by the VWF-cleaving metalloprotease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif 13). Furthermore, ADAMTS13-deficient mice with high baseline VWF (ADAMTS13-/-/casa) developed a preeclampsia-like condition spontaneously, with VWF adhesive activity increasing 5.6-fold and placenta-derived extracellular vesicles increasing 2.9-fold during late pregnancy. VWF became hyperadhesive during pregnancy by undergoing conformational changes and promoted preeclampsia-associated endotheliopathy by enhancing the interaction of placenta-derived extracellular vesicles with endothelial cells.

Conclusions: This study demonstrates that hyperadhesive VWF plays a causal role in preeclampsia and is a potential therapeutic target.

Keywords

Female, Animals, Pregnancy, Pre-Eclampsia, von Willebrand Factor, Humans, ADAMTS13 Protein, Disease Models, Animal, Mice, Knockout, Placenta, Mice, Inbred C57BL, Extracellular Vesicles, Cell Adhesion, Endothelial Cells, Cells, Cultured, Mice, endothelial cells, extracellular vesicles, pre-eclampsia, pregnancy, von Willebrand Factor

Published Open-Access

yes

Recommended Citation

Wang, Yajuan; Wang, Chenyu; Houck, Katie L; et al., "Hyperadhesive von Willebrand Factor Contributes to Pathogenesis of Preeclampsia" (2026). Children’s Nutrition Research Center Staff Publications. 420.
https://digitalcommons.library.tmc.edu/staff_pub/420