MMP-13 binds to platelet receptors αIIbβ3 and GPVI and impairs aggregation and thrombus formation
Joanna-Marie Howes1, Nicholas Pugh2, Samir W Hamaia1
1Department of Biochemistry University of Cambridge Cambridge UK.
Insights
Matrix metalloproteinase-13 (MMP-13) inhibits platelet aggregation and thrombus formation by binding to platelet receptors. This discovery offers new insights into atherothrombotic pathologies.
Area of Science:
- Cardiovascular Biology
- Thrombosis Research
- Molecular Medicine
Background:
- Atherosclerotic plaque rupture triggers thrombus formation, leading to myocardial infarction and stroke.
- Collagen exposure during plaque rupture activates platelets, initiating aggregation.
- Other plaque components can influence platelet function and thrombus development.
Purpose of the Study:
- To investigate the role of matrix metalloproteinase-13 (MMP-13) in platelet aggregation and thrombus formation.
- To determine if MMP-13, upregulated in atherothrombotic conditions, impacts platelet function.
Main Methods:
- Assessed MMP-13 binding to platelet receptors alphaIIbbeta3 (αIIbβ3) and glycoprotein (GP)VI.
- Evaluated the effect of MMP-13 on washed platelet aggregation.
- Measured thrombus formation on fibrillar collagen in flowing blood.
Main Results:
- MMP-13 binds to platelet receptors αIIbβ3 and GPVI.
- MMP-13 significantly inhibits washed platelet aggregation.
- MMP-13 decreases thrombus formation on fibrillar collagen.
Conclusions:
- MMP-13 inhibits platelet aggregation and thrombus formation in flowing blood.
- MMP-13 may play a subtle role in atherothrombotic pathologies.
- Findings suggest new research avenues for understanding MMP-13's mechanisms in cardiovascular disease.
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.
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