What thrombogenic substance is produced and released by endothelial cells (ECs)?

Von Willebrand Factor is the Thrombogenic Substance Produced by Endothelial Cells

Among the options provided, von Willebrand factor (VWF) is the thrombogenic substance that is produced and released by endothelial cells.

Analysis of Each Option

B. Von Willebrand Factor ✓

Von Willebrand factor is synthesized in endothelial cells and stored in specialized organelles called Weibel-Palade bodies, from which it is released into circulation under various stimuli 1. It is an essential hemostatic protein that contributes to thrombosis by:

• Promoting platelet adhesion by anchoring platelets to the subendothelial matrix 1, 2
• Serving as a carrier molecule for factor VIII in circulation 2, 3
• Unfolding under high shear stress conditions to bind platelets and subendothelial matrix 2
• Contributing to the pathogenesis of disseminated intravascular coagulation (DIC) 1

Endothelial cells are the primary source of VWF, although it is also produced in megakaryocytes and stored in platelet alpha granules 1, 4.

A. Thromboxane A2 ✗

Thromboxane A2 is primarily produced by activated platelets, not endothelial cells 1. It functions as a platelet aggregator and is increased in certain conditions like polycythemia vera, but it is not an endothelial cell product 1.

C. Thrombin ✗

Thrombin (activated factor II) is not produced by endothelial cells. It is generated in the coagulation cascade through the activation of prothrombin by factor Xa. Endothelial cells interact with thrombin through thrombomodulin, which converts thrombin's activity from prothrombotic to antithrombotic 1.

D. Tissue Plasminogen Activator ✗

While tissue plasminogen activator (t-PA) is indeed produced by endothelial cells, it is not a thrombogenic substance. Rather, t-PA is a fibrinolytic agent that activates plasminogen to plasmin, which degrades fibrin clots 1, 5. It has anti-thrombotic rather than thrombogenic properties.

Endothelial Cell Function in Hemostasis

Endothelial cells play a dual role in hemostasis:

• Prothrombotic factors produced by endothelial cells include:

  • Von Willebrand factor 1, 2
  • Tissue factor (under inflammatory conditions) 5
  • Plasminogen activator inhibitor-1 (PAI-1) 5

• Antithrombotic factors produced by endothelial cells include:

  • Thrombomodulin 1
  • Tissue plasminogen activator 5
  • Prostacyclin 5
  • Heparan sulfate 5

Clinical Significance

The production of VWF by endothelial cells has important clinical implications:

• Elevated VWF levels serve as a biomarker for endothelial activation in conditions like DIC, sepsis, and thrombotic disorders 1
• VWF levels can predict severity and outcomes in sepsis-associated DIC 1
• Deficiency or dysfunction of VWF leads to von Willebrand Disease (VWD), the most common inherited bleeding disorder 2
• VWF plays a role in inflammatory processes by recruiting leukocytes and directing the formation of Weibel-Palade bodies that contain inflammatory mediators like P-selectin 6

In summary, von Willebrand factor is the correct answer as it is the only thrombogenic substance among the options that is produced and released by endothelial cells.