Activated protein C

Activated Protein C (APC) is a protein that plays a crucial role in regulating blood coagulation, inflammation, and maintaining the permeability of blood vessel walls. It is an enzyme that is derived from its precursor, protein C, which is a vitamin K-dependent protein synthesized in the liver. The activation of protein C is a critical step in the anticoagulation pathway, which helps to prevent the formation of dangerous blood clots (thrombosis) and to protect the body against excessive inflammation.

Activation

The activation of protein C occurs on the endothelial cell surface, which lines the blood vessels, where it is converted by the thrombin-thrombomodulin complex into its active form, APC. This process is greatly enhanced in the presence of Endothelial Protein C Receptor (EPCR), which binds protein C and presents it to the thrombin-thrombomodulin complex.

Mechanism of Action

Once activated, APC exerts its anticoagulant effect primarily by inactivating Factors Va and VIIIa in the coagulation cascade, thereby reducing the generation of thrombin. In addition to its anticoagulant properties, APC also has anti-inflammatory effects, promotes fibrinolysis (the breakdown of fibrin clots), and has cytoprotective effects that help to maintain the integrity of the endothelial barrier.

Clinical Significance

The importance of APC in controlling coagulation and inflammation makes it a target for therapeutic intervention in various conditions. Deficiency in protein C or its function leads to an increased risk of venous thrombosis, while excessive activation can contribute to bleeding disorders. Recombinant forms of APC, such as Drotrecogin alfa (activated), have been explored for the treatment of severe sepsis and septic shock, conditions characterized by dysregulated inflammation and coagulation, although its use has been controversial and is no longer widely recommended.

Genetic Aspects

Mutations in the PROC gene, which encodes protein C, can lead to protein C deficiency, a condition associated with an increased risk of venous thromboembolism. The severity of the condition can vary depending on whether the deficiency is heterozygous or homozygous, with the latter being more severe and often presenting in neonates as Purpura fulminans, a rapidly progressive thrombotic disorder.

Conclusion

Activated Protein C plays a vital role in the body's defense mechanism against thrombosis and inflammation. Its activities span the regulation of coagulation, inflammation, fibrinolysis, and endothelial cell function, highlighting its importance in maintaining vascular health and homeostasis. Ongoing research continues to explore its potential therapeutic applications and the implications of its dysfunction in various diseases.