Apoptotic vascular endothelial cells become procoagulant

Area of Science:

• Vascular Biology
• Cellular Biology
• Hemostasis and Thrombosis

Background:

• Endothelial cells normally exhibit anticoagulant properties.
• Inflammatory and atherogenic stimuli can shift endothelial cells towards a procoagulant state.
• Apoptosis of vascular cells is observed in conditions like atherosclerosis and inflammation.

Purpose of the Study:

• To investigate if apoptotic endothelial cells contribute to a prothrombotic state.
• To determine the procoagulant mechanisms of apoptotic endothelial cells.

Main Methods:

• Induction of apoptosis in human umbilical vein endothelial cells (HUVECs) using staurosporine or serum deprivation.
• Assessment of phosphatidylserine (PS) exposure via flow cytometry (annexin V binding).
• Measurement of tissue factor (TF) activity, thrombomodulin, heparan sulfates, and TF pathway inhibitor levels and function.

Main Results:

• Apoptotic HUVECs (both adherent and detached) exhibited increased procoagulant activity.
• Phosphatidylserine exposure on apoptotic HUVECs enhanced intrinsic tenase complex activity.
• Loss of anticoagulant membrane components (thrombomodulin, heparan sulfates, TFPI) was observed.
• Apoptotic HUVECs significantly increased thrombin formation in plasma.

Conclusions:

• Apoptotic endothelial cells acquire a procoagulant phenotype.
• This shift is mediated by phosphatidylserine exposure and reduced anticoagulant surface molecules.
• Apoptotic endothelial cells may play a role in the development of thrombosis.