title: Emerging role of serpinE2/protease nexin-1 in hemostasis and vascular biology.
abstract: Serine protease inhibitors, termed serpins, are key regulators in many biologic events. Protease nexin-1 (PN-1) is a serpin that is barely detectable in plasma but found in many organs and produced by most cell types, including monocytes, platelets, and vascular cells. It has a large inhibition spectrum because it is the most efficient tissue inhibitor of thrombin but also a powerful inhibitor of plasminogen activators and plasmin. It has a high affinity for glycosaminoglycans, such as heparan sulfates, which potentiate its activity toward thrombin and target it to the pericellular space. PN-1 has been previously largely described as a crucial regulator of the proteolytic activity in nerves and of central and peripheral nervous system function. In contrast, little was known about its involvement in hemostasis and vascular biology. This article reviews recent data underlining its emerging role as a key factor in the responses of vessels to injury. Indeed, studies of PN-1-deficient mice have established important antithrombotic and antifibrinolytic properties of this serpin that have heretofore gone unrecognized. The roles of PN-1 in the areas of hemostasis and thrombosis summarized here provide insights that may allow the development of drugs and treatment strategies to prevent or limit thrombotic disorders.
authors.affiliation: Inserm U698, Université Paris Diderot, Paris, France. marie-christine.bouton@inserm.fr
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Bouton
authors.forename: Yacine
authors.initials: Y
authors.lastname: Boulaftali
authors.forename: Benjamin
authors.initials: B
authors.lastname: Richard
authors.forename: Véronique
authors.initials: V
authors.lastname: Arocas
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Michel
authors.forename: Martine
authors.initials: M
authors.lastname: Jandrot-Perrus
mesh_terms: D000818:Animals; D006487:Hemostasis; D006801:Humans; D051379:Mice; D058258:Serpin E2 / Q000378:metabolism*; D013927:Thrombosis / Q000201:enzymology / Q000209:etiology* / Q000473:pathology*
chemical_list: D058258:Serpin E2