dc.description.abstract | The coagulation cascade consists of several factors that all contribute to the balance between bleeding and haemostasis. Protein C (PC) and protein S (PS) are two of these factors, which both are known for their anticoagulant function. Activated PC (APC) is able to cleave activated factor V (FVa) and VIII (FVIIIa), whereas PS acts as a cofactor for both anticoagulant factors PC and tissue factor pathway inhibitor (TFPI). In addition to these well-known anticoagulant functions both PC and PS have several other functions. APC is shown to be able to act anti-inflammatory and anti-apoptotic, via activation of protease-activated receptor 1 (PAR1). Via activation of Tyro3, Axl and Mer (TAM) receptors, PS has anti-inflammatory functions and is involved in angiogenesis.
As anticoagulant factors, both PC and PS are known to be involved in the coagulation-related diseases thrombosis, purpura fulminans and atherosclerosis. In addition PC and PS play also a role in inflammation-related diseases, such as sepsis, systemic lupus erythematous (SLE), human immunodeficiency virus (HIV) and non-alcoholic fatty liver disease (NAFLD). The beneficial role of PC in sepsis even led to the development of (A)PC based treatments.
Via distinct signalling routes both PC and PS enhance the blood-brain barrier (BBB) integrity and thereby decrease the risk on neurological diseases. Besides, by crossing the BBB, APC is shown to play a role in the two neurodegenerative diseases, amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) and in stroke. At last, APC is found to play a role in cancer, but for PS the role in this disease is still unclear. Associations between PC and PS deficiencies and coagulation-related and inflammation-related diseases confirm the role of PC and PS in these type of diseases. | |