IWR-1 Inhibits Collagen-Induced Platelet Activation and Protects against Thrombogenesis.

IWR-1 Inhibits Collagen-Induced Platelet Activation and Protects against Thrombogenesis.
Hamostaseologie. 2019 Mar 08;:
Authors: Wang W, Lai S, Xiao Z, Yan H, Li Y, Zhang Y, Wu Y, Wang L
Abstract
Platelets play a crucial role in haemostasis and several pathophysiological processes. Collagen is a main initiator for platelet activation and aggregation. Given that Wnt signalling negatively regulates platelet function, and IWR-1 (a small molecule inhibitor for Wnt signalling) has the potential of inhibiting collagen synthesis, it is essential to investigate whether IWR-1 regulates collagen-induced platelet activation and protects against thrombogenesis. In the present study we found that IWR-1 pretreatment effectively suppressed collagen-induced platelet aggregation in a dose-dependent manner. In addition, IWR-1 also resulted in a decrease of P-selectin and phosphatidylserine surface exposure using fluorescence-activated cell sorting analysis. In vitro studies further revealed that IWR-1 had a negative effect on integrin a2β1 activation and platelet spreading. More importantly, the results from in vivo studies showed that IWR-1 exhibited a robust bleeding diathesis in the tail-bleeding assay and a prolonged occlusion time in the FeCl3-induced carotid injury model. Taken together, current results demonstrate that IWR-1 could effectively block collagen-induced platelet activity in vitro and in vivo, and suggest its candidacy as a new anti...

Source: Hamostaseologie - March 7, 2019 Category: Hematology Authors: Wang W, Lai S, Xiao Z, Yan H, Li Y, Zhang Y, Wu Y, Wang L Tags: Hamostaseologie Source Type: research