Modified platelet deposition on MMP-13 digested collagen I
Journal of Thrombosis and Haemostasis
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Dear, J., Pugh, N., Knäuper, V., & Farndale, R. (2015). Modified platelet deposition on MMP-13 digested collagen I. Journal of Thrombosis and Haemostasis, 13 2253-2259. https://doi.org/10.1111/jth.13166
BACKGROUND: Atherothrombosis underlies acute coronary syndromes, including unstable angina and acute myocardial infarction. Within the unstable plaque, monocytes express collagenolytic matrix metalloproteinases (MMPs) including MMP-13 which degrades fibrous collagen. Following rupture, vessel wall components including degraded collagen are exposed to circulating platelets. Platelet receptors then mediate the recruitment and activation of platelets to form a thrombus, blocking blood flow and resulting in myocardial infarction and sudden death. OBJECTIVES: Here we aim to provide information on the effects of collagen degradation on platelet adhesion and thrombus formation. METHODS: Using increasing concentrations of MMP-13, we induced progressive degradation of fibrous and monomeric collagen I, visualised by electrophoresis, and then investigated the capacity of the resulting fragments to support static platelet adhesion and thrombus formation in whole flowing blood. RESULTS: Both integrin and Glycoprotein VI-dependent interactions with fibrous collagen underpin high levels of platelet adhesion under both conditions, with little obvious effect of MMP-13 treatment. Static platelet adhesion to monomeric collagen was strongly α2β1- dependent regardless of degradation status. Under flow conditions, partially degraded monomeric collagen supported increased thrombus deposition at 10 µg/ml MMP-13; falling close to background when collagen degradation was complete (100 µg/ml MMP-13). CONCLUSIONS: New binding activities come into play after partial digestion of collagen monomers, and net platelet-reactivity through all axes is abolished as degradation becomes more complete.
Matrix Metalloproteinase 13, collagen, collagenase, platelets, GPVI collagen receptor
This work was supported by the British Heart Foundation (RG/009/003/27122) and the Wellcome Trust (094470/Z/10/Z).
British Heart Foundation (RG/09/003/27122)
Wellcome Trust (094470/Z/10/Z)
British Heart Foundation (RG/15/4/31268)
External DOI: https://doi.org/10.1111/jth.13166
This record's URL: https://www.repository.cam.ac.uk/handle/1810/251159
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