当前位置： SCI文献检索 > THROMBOSIS AND HAEMOSTASIS期刊下所有文献 > Protease-Activated Receptor PAR-4: An Inducible Switch between Thrombosis and Vascular Inflammation?

Protease-Activated Receptor PAR-4: An Inducible Switch between Thrombosis and Vascular Inflammation?

Abstract：

:Thrombin triggers activation of platelets through protease-activated receptor 1 (PAR-1) and PAR-4. Both receptors are widely expressed and exert multiple platelet-independent functions. PAR signalling contributes to healing responses after injury, by promoting cytokine activity and cellular growth and mobility. Uncontrolled PAR activation, however, can prevent timely resolution of inflammation, enhance thrombogenic endothelial function and drive adverse remodelling. The specific role of PAR-4 in thromboinflammatory vascular disease has been largely underestimated, given the relatively limited expression of PAR-4 in non-platelet cells under healthy conditions. However, unlike PAR-1, PAR-4 expression adapts dynamically to numerous stimuli associated with thromboinflammation, including thrombin, angiotensin II, sphingosine-1-phosphate (S1P), high glucose and redox stress, suggesting expression is switched on 'at need'. Prostacyclin negatively regulates PAR-4 expression at the post-transcriptional level, which may serve to fine-tune thrombin responses and limit these to the injury site. PAR-4 elicits inflammatory, mitogenic and proliferative actions not only in response to thrombin but also to numerous other inflammatory proteases, and can cross-talk with other receptor systems such as S1P and adenosine receptors. Accordingly, PAR-4 has emerged as a candidate player in vessel disease and cardiac post-infarction remodelling. Currently, PAR-4 is a particularly promising target for safer anti-thrombotic therapies. Recent studies with the PAR-4 antagonist BMS-986120 lend support to the concept that selective antagonism of PAR-4 may offer both an effective and safe anti-thrombotic therapy in the acute thrombotic setting as well as an anti-inflammatory strategy to prevent long-term progressive atherosclerotic disease in high-risk cardiovascular patients.

journal_name

Thromb Haemost

journal_title

Thrombosis and haemostasis

authors

Fender AC,Rauch BH,Geisler T,Schrör K

doi

10.1160/TH17-03-0219

subject

Has Abstract

pub_date

2017-11-01 00:00:00

pages

2013-2025

issue

eissn

0340-6245

issn

2567-689X

journal_volume

117

pub_type

杂志文章,评审

在线工具

Protease-Activated Receptor PAR-4: An Inducible Switch between Thrombosis and Vascular Inflammation?