Vitamin E Protects Against Gestational Deep Vein Thrombosis: The Role of Inhibiting Endothelial Ferroptosis

This study aimed to investigate the effect of vitamin E on deep vein thrombosis (DVT) during pregnancy, including its impact on inflammation, coagulation, thrombus recanalization and pregnancy outcomes, and to explore the potential mechanism related to ferroptosis.

A rat model of pregnancy-associated DVT was established using the "stenosis" method. We analyzed the effects of vitamin E on thrombus morphology, inflammation, coagulation function, pregnancy outcomes, and angiogenesis, alongside assessing ferroptosis levels in thrombotic tissues. In vitro, ferroptosis was induced in human umbilical vein endothelial cells using Erastin. The effects of vitamin E treatment on endothelial cell biological behaviors (proliferation, migration, invasion, tube formation) and ferroptosis status were evaluated.

Vitamin E treatment significantly reduced thrombus size, decreased neutrophil count, neutrophil percentage, platelet count, interleukin-6, and interferon-γ levels, and increased the number of live births and placental efficiency, with no effect on coagulation. It promoted thrombus dissolution and recanalization. Furthermore, vitamin E significantly decreased ferroptosis levels. In vitro, Erastin successfully induced endothelial cell ferroptosis. Vitamin E treatment significantly promoted the proliferation, migration, invasion, and tube formation of injured endothelial cells. It also markedly reduced the levels of reactive oxygen species and malondialdehyde, decreased the number of damaged mitochondria, and substantially alleviated ferroptosis in the injured endothelial cells.

Vitamin E significantly promoted the dissolution and recanalization of DVT during pregnancy, potentially by reducing endothelial cell ferroptosis. This study provides a new therapeutic strategy and insights into the mechanism for managing pregnancy-associated DVT.