Related Experiment Video
Updated: Jul 23, 2025

Deep Vein Thrombosis Induced by Stasis in Mice Monitored by High Frequency Ultrasonography
Published on: April 13, 2018
Deep Vein Thrombosis Is Facilitated by Endothelial-Derived Extracellular Vesicles via the PDI-GRP94-GPIIb/IIIa
Hongtao Lan1,2, Zhoujie Tong1, Yaqiong Jiao3
1The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Cheeloo College of Medicine, Qilu Hospital, Shandong University, Chinese National Health Commission and Chinese Academy of Medical Sciences, Jinan 250012, China.
Aims:
Deep vein thrombosis (DVT) is a prevalent cardiovascular condition. Endothelial-derived extracellular vesicles (EVs) may play a crucial role in platelet-dependent DVT development via platelet activation, but the mechanism is not clear yet. This research aims to understand how platelets and endothelial-derived EVs work in DVT.
Methods:
The interaction between protein disulfide isomerase (PDI) and glucose-regulated protein 94 (GRP94) was founded by molecular docking. Inferior vena cava stasis-induced mice received PDI and GRP94 inhibitor treatments. Platelet activation, endothelial-derived EVs, and PDI were measured using flow cytometry. The expression of PDI and dimetric GRP94 in platelets co-cultured with hypoxic endothelial cells was confirmed by Western blot or native PAGE. The fluorescence resonance energy transfer assay shows conformational changes in GPIIb/IIIa on platelet surfaces. A tracking experiment was performed using PKH26, which labelled endothelial-derived EVs, and the endocytosis of EVs by platelets was tracked by confocal microscope.
Results:
In a DVT mouse model, platelets enhance venous thrombus formation in a coagulation-independent manner, instead, platelet activation and the length of the thrombus are related to PDI and GRP94 activity. Next, we found that the expression level of endothelial-derived EVs carrying PDI is significantly increased in plasma. Endothelial-derived EVs carrying PDI are endocytosed by platelets, in which the content of GRP94 dimer is elevated, and consequently increases the expression of surface GPIIb/IIIa. In addition, PDI allosterically interacts with GPIIb/IIIa, which is re-configurated into an activated form.
Conclusion:
Endothelial-derived EVs carrying PDI induce DVT via interplay with GRP94 and GPIIb/IIIa in platelets. These findings emphasize the significance of platelets in DVT formation, and PDI may be a suitable target in DVT prevention.
Related Concept Videos
Venous Thrombosis I: Introduction
Venous Thrombosis III: Interprofessional Care
Anticoagulant Drugs: Low-Molecular-Weight Heparins
Extrinsic and Intrinsic Pathways of Hemostasis
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which...
Intracellular Signaling Affects Focal Adhesions
Some...
Formation of the Platelet Plug
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...

