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MMP ‐13 binds to platelet receptors α II bβ3 and GPVI and impairs aggregation and thrombus formation
Author(s) -
Howes JoannaMarie,
Pugh Nicholas,
Hamaia Samir W.,
Jung Stephanie M.,
Knäuper Vera,
Malcor JeanDaniel,
Farndale Richard W.
Publication year - 2018
Publication title -
research and practice in thrombosis and haemostasis
Language(s) - English
Resource type - Journals
ISSN - 2475-0379
DOI - 10.1002/rth2.12088
Subject(s) - gpvi , thrombus , platelet aggregation , platelet , receptor , chemistry , microbiology and biotechnology , biophysics , platelet membrane glycoprotein , biochemistry , medicine , biology
Essentials MMP‐13 has the potential to influence platelet function and thrombus formation directly. We sought to elucidate whether MMP‐13 is able to bind to specific platelet receptors. MMP‐13 is able to bind to platelet alphaIIbbeta3 (αIIbβ3) and glycoprotein (GP)VI. These interactions are sufficient to inhibit platelet aggregation and thrombus formation.Background Acute thrombotic syndromes lead to atherosclerotic plaque rupture with subsequent thrombus formation, myocardial infarction and stroke. Following rupture, flowing blood is exposed to plaque components, including collagen, which triggers platelet activation and aggregation. However, plaque rupture releases other components into the surrounding vessel which have the potential to influence platelet function and thrombus formation. Objectives Here we sought to elucidate whether matrix metalloproteinase‐13 ( MMP ‐13), a collagenolytic metalloproteinase up‐regulated in atherothrombotic and inflammatory conditions, affects platelet aggregation and thrombus formation. Results We demonstrate that MMP ‐13 is able to bind to platelet receptors alpha II bbeta3 (α II bβ3) and platelet glycoprotein ( GP ) VI . The interactions between MMP ‐13, GPVI and α II bβ3 are sufficient to significantly inhibit washed platelet aggregation and decrease thrombus formation on fibrillar collagen. Conclusions Our data demonstrate a role for MMP ‐13 in the inhibition of both platelet aggregation and thrombus formation in whole flowing blood, and may provide new avenues of research into the mechanisms underlying the subtle role of MMP ‐13 in atherothrombotic pathologies.

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