Volumen: 17 # Number : Suplemento
Publication Date : Octubre Year: 2013
Downregulation of the clotting
cascade by the protein C
Authors: F. Stavenuiter, E.A.M. Bouwens, L.O. Mosnier
Abstract: The protein C pathway provides important biological
activities to maintain the fluidity of the circulation,
prevent thrombosis, and protect the integrity of the vasculature in response to injury. Activated protein C (APC), in concert with its co-factors and cell receptors, assembles in specific macromolecular complexes to provide efficient proteolysis of multiple substrates that result in anticoagulant and cytoprotective
activities. Numerous studies on APC’s structure-
function relation with its co-factors, cell receptors,
and substrates provide valuable insights into the molecular mechanisms and presumed assembly of the macromolecular complexes that are responsible for APC’s activities. These insights allow for molecular
engineering approaches specifically targeting the interaction of APC with one of its substrates or co-factors. Thus far, these approaches resulted in several anticoagulant-selective and cytoprotective-selective APC mutants, which provide unique insights into the relative contributions of APC’s anticoagulant or cytoprotective activities to the beneficial effects of APC in various murine injury and disease models. Because of its multiple physiological and pharmacological
activities, the anticoagulant and cytoprotective
protein C pathway have important implications for the (patho)physiology of vascular disease and for translational research exploring novel therapeutic
strategies to combat complex medical disorders such as thrombosis, inflammation, ischemic stroke and neurodegenerative disease.
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