Stimulation of XXXX production contributes to the antiplatelet and antithrombotic effect of new peptide pENW (pGlu-Asn-Trp).

@entity24871 @entity70567 @entity1423 @entity1854 @entity4982 @entity842 @entity432 @entity35 @entity715 @entity857 @entity6462
INTRODUCTION: New peptide @entity70567 (pENW), initially extracted from snake venom, significantly attenuates the formation of arterial and venous thrombi in vivo, and has modest in-vitro antiplatelet activity. This study was designed to investigate the underlying mechanisms. METHODS: The @entity35 carotid @entity715 model induced by @entity24871 was established to evaluate the antithrombotic activity of pENW. The effects of pENW on the production of @entity842 (NO), as well as the expression and activity of endothelial @entity842 synthase (eNOS), were determined. The vasorelaxant effect of pENW was evaluated using isolated @entity35 aortic rings in the absence or presence of @entity6462 ( @entity6462 , eNOS inhibitor). Furthermore, the in-vitro antiplatelet activity of pENW was investigated with the addition of @entity1854 ( @entity4982 , NO donor) and/or @entity6462 to further prove the role of NO and eNOS in the inhibitory effect of pENW on @entity1423 . RESULTS: In vivo, pENW inhibited @entity715 formation induced by endothelial injury in a dose-dependent manner, with a significantly prolonged time to the occurrence of @entity432 . It was shown that pENW offered protection for blood vessels from oxidative injury. pENW significantly increased NO production in @entity35 treated with pENW at 4 or 2mg/kg body weight. Furthermore, the production of NO from the cultured vascular endothelial cells was increased with the treatment of 10(-4)M and 10(-5)M pENW; pENW also enhanced eNOS expression and activity both in vivo and in vitro, and elicited a concentration-dependent vasorelaxation which was significantly inhibited by @entity6462 . Notably, pENW inhibited @entity857 -induced @entity1423 , and the inhibition was more significant in the presence of NO. The inhibition of @entity1423 by pENW was significantly abolished by @entity6462 . CONCLUSIONS: The in-vivo antiplatelet and antithrombotic effects of pENW are at least partly mediated by the increased production of endogenous NO via up-regulation and stimulation of eNOS. The findings suggest that pENW could potentially be developed as a novel therapeutic agent in the treatment of platelet-driven disorders.
