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 antiplatelet agent.
Keywords
IWR-1 - collagen - platelet activation - thrombogenesis
