Anticoagulant and antithrombotic properties of platelet protease nexin-1

作者：Boulaftali Yacine; Adam Frederic; Venisse Laurence; Ollivier Veronique; Richard Benjamin; Taieb Sabrina; Monard Denis; Favier Remi; Alessi Marie Christine; Bryckaert Marijke; Arocas Veronique; Jandrot Perrus Martine; Bouton Marie Christine^*

来源：Blood, 2010, 115(1): 97-106.

DOI：10.1182/blood-2009-04-217240

Protease nexin-1 (PN-1) is a serpin that inhibits plasminogen activators, plasmin, and thrombin. PN-1 is barely detectable in plasma but is expressed by platelets. Here, we studied platelet PN-1 in resting and activated conditions and its function in thrombosis. Studies on human platelets from healthy donors and from patients with a Gray platelet syndrome demonstrate that PN-1 is present both at the platelet surface and in alpha-granules. The role of PN-1 was investigated in vitro using human platelets incubated with a blocking antibody and using platelets from PN-1-deficient mice. Both approaches indicate that platelet PN-1 is active on thrombin and urokinase-type plasminogen activator. Blockade and deficiency of platelet PN-1 result in accelerated and increased tissue factor-induced thrombin generation as indicated by calibrated automated thrombography. Moreover, platelets from PN-1-deficient mice respond to subthreshold doses of thrombin, as assessed by P-selectin expression and platelet aggregation. Thrombus formation, induced ex vivo by collagen in blood flow conditions and in vivo by FeCl(3)-induced injury, is significantly increased in PN-1-deficient mice, demonstrating the antithrombotic properties of platelet PN-1. Platelet PN-1 is thus a key player in the thrombotic process, whose negative regulatory role has been, up to now, markedly underestimated. (Blood. 2010;115:97-106)

• 出版日期2010-1-7