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Hamostaseologie 2019; 39(04): 392-397
DOI: 10.1055/s-0038-1676822
Original Article
Georg Thieme Verlag KG Stuttgart · New York

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

Wei Wang
1   Department of Emergency and Critical Care Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, China
,
Songqing Lai
2   Department of Cardiothoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, China
,
ZiJin Xiao
3   The Attached Middle School to Jiangxi Normal University, Nanchang City, Jiangxi Province, China
,
Haiyue Yan
4   Nanjing Foreign Language School, Nanjing City, Jiangsu Province, China
,
Yongxi Li
5   Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, China
,
Ye Zhang
1   Department of Emergency and Critical Care Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, China
,
Yanqing Wu   ∗
5   Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, China
,
Ling Wang   ∗
6   Department of Medicine Lab, The Second Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, China
› Author Affiliations
Further Information

Publication History

06 July 2018

03 November 2018

Publication Date:
08 March 2019 (online)

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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

∗ Note: Yanqing Wu and Ling Wang have made equally important and outstanding contributions to this paper and thus share senior authorship.


Supplementary Material

 

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