Protein C is a compound present in the human body that exists in either an inactive or activated state. In its activated state, protein C plays an essential role in several important biological functions including blood clotting and programmed cell death. Also know as autoprothrombin IIA and blood coagulation factor XIV, the protein in its inactive state is made up of over 400 amino acids and relies on the presence of substances such as thrombomodulin in the blood stream for its activation. It is produced in the liver, and deficiencies may cause several serious, often fatal, conditions. The protein has been used as a therapeutic treatment in the past but has largely fallen from favor due to the associated severe bleeding risks involved.
Under normal conditions, protein C is a zymogenic or inactive agent that requires the presence of certain biological precursors to become active. Once activated, protein C plays a key role in facilitating a number of critical biological functions relating to blood coagulation. These functions include the regulation of blood clotting, inflammation, blood vessel wall permeability and apoptosis or programmed cell death (PCD). When inactive, protein C is a complex, dual chain combination of 419 amino acids linked by a peptide activator. The previously mentioned biological precursors, such as thrombomodulin and endothelial protein C receptor (EPCR), act on this peptide link, thereby splitting the chain and activating the protein.
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The activated protein C (APC) then goes to work at suppressing other agents in the bloodstream to achieve its anticoagulant and anti-inflammatory functions. The critical role that APC plays in these essential processes makes deficiencies in the natural production of the protein particularly dangerous. Persons with impaired production levels of the protein suffer from a significant increase in the risk of potentially fatal thrombosis or blood clot formation. Deficiencies in the production of the protein are typically the result of genetic factors; lifestyle and diet generally play insignificant roles. A condition known as activated protein C resistance which impairs the efficacy of the activated protein can also cause APC deficiency type conditions.
Therapeutic applications of APC have been used in several trials to treat conditions such as lung injuries, ischemic strokes, severe sepsis, and type 1 diabetes. It has also been investigated as an aid in improving the outcomes in pancreatic islet transplants. Although the results have been generally encouraging, the potential of resultant uncontrollable bleeding makes it unrealistically risky in many cases.