However, a 2012 Cochrane review found that its use cannot be recommended since it does not improve survival and increases bleeding risk. Eli Lilly ran an aggressive marketing campaign to promote its use for people with severe sepsis and septic shock and sponsored the 2004 Surviving Sepsis Campaign Guidelines. Research into the clinical use of a recombinant form of human Activated Protein C (rhAPC) known as Drotrecogin alfa-activated, branded Xigris by Eli Lilly and Company, has been surrounded by controversy. : 34 : 3162 Because of the crucial role that protein C plays as an anticoagulant, those with deficiencies in protein C, or some kind of resistance to APC, suffer from a significantly increased risk of forming dangerous blood clots ( thrombosis). Because of EPCR's role, activated protein C is found primarily near endothelial cells (i.e., those that make up the walls of blood vessels), and it is these cells and leukocytes (white blood cells) that APC affects. : 4673 The protein C zymogen is activated when it binds to thrombin, another protein heavily involved in coagulation, and protein C's activation is greatly promoted by the presence of thrombomodulin and endothelial protein C receptors (EPCRs). Its structure is that of a two-chain polypeptide consisting of a light chain and a heavy chain connected by a disulfide bond. The zymogenic form of protein C is a vitamin K-dependent glycoprotein that circulates in blood plasma. : 35 In humans, protein C is encoded by the PROC gene, which is found on chromosome 2. APC is classified as a serine protease since it contains a residue of serine in its active site. Activated protein C ( APC) performs these operations primarily by proteolytically inactivating proteins Factor V a and Factor VIII a. The activated form plays an important role in regulating anticoagulation, inflammation, and cell death and maintaining the permeability of blood vessel walls in humans and other animals. Protein C, also known as autoprothrombin IIA and blood coagulation factor XIX, : 6822 is a zymogen, that is, an inactive enzyme.
endoplasmic reticulum to Golgi vesicle-mediated transport.positive regulation of establishment of endothelial barrier.negative regulation of apoptotic process.
negative regulation of blood coagulation.
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