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BIOLOGICHESKIE MEMBRANY

Journal of Membrane and Cell Biology

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The Effect of Oxidative Stress on the Transport of the P-Glycoprotein Substrate through the Cell Monolayer

A. V. Shchulkin, Yu. V. Abalenikhina, E. N. Yakusheva

Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology. 2021;15(3):257-269

Pages: 257-269

Abstract

Extracellular vesicles (EVs) are nanosized, membrane-bound particles released by various cell types that play a critical role in intercellular communication and hemostasis. The procoagulant properties of EVs, primarily mediated by the exposure of phosphatidylserine on their surface and the presence of tissue factor (TF), are essential for maintaining the delicate balance of the coagulation cascade. This study investigates the procoagulant potential of circulating EVs in both normal, uncomplicated pregnancies and those complicated by pathological conditions, such as preeclampsia (PE) and intrauterine growth restriction (IUGR). We hypothesize that alterations in the concentration, cellular origin, and procoagulant activity of EVs contribute to the hypercoagulable state characteristic of pathological pregnancy. Using flow cytometry and thrombin generation assays, we quantified the levels of platelet-derived, endothelial-derived, and placental-derived EVs and assessed their capacity to accelerate coagulation. Our findings indicate a significant increase in the total number and procoagulant activity of circulating EVs in pathological pregnancies compared to normal controls, particularly those expressing TF. These results suggest that the dysregulated release of highly procoagulant EVs may serve as a critical mechanism driving thrombotic complications in adverse pregnancy outcomes, highlighting their potential as diagnostic biomarkers and therapeutic targets.

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