MMP-13 binds to platelet receptors αIIbβ3 and GPVI and impairs aggregation and thrombus formation.

Autor: Howes JM; Department of Biochemistry University of Cambridge Cambridge UK., Pugh N; Department of Biomedical and Forensic Sciences Anglia Ruskin University Cambridge UK., Hamaia SW; Department of Biochemistry University of Cambridge Cambridge UK., Jung SM; Department of Biochemistry University of Cambridge Cambridge UK., Knäuper V; Cardiff University Dental School Cardiff UK., Malcor JD; Department of Biochemistry University of Cambridge Cambridge UK., Farndale RW; Department of Biochemistry University of Cambridge Cambridge UK.
Jazyk: angličtina
Zdroj: Research and practice in thrombosis and haemostasis [Res Pract Thromb Haemost] 2018 Mar 25; Vol. 2 (2), pp. 370-379. Date of Electronic Publication: 2018 Mar 25 (Print Publication: 2018).
DOI: 10.1002/rth2.12088
Abstrakt: 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 alphaIIbbeta3 (αIIbβ3) and platelet glycoprotein (GP)VI. The interactions between MMP-13, GPVI and αIIbβ3 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.
Databáze: MEDLINE
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