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Modified platelet deposition on MMP-13 digested collagen I

Howes, Joanna-Marie, Pugh, Nicholas, Knauper, Vera and Farndale, Richard W. 2015. Modified platelet deposition on MMP-13 digested collagen I. Journal of Thrombosis and Haemostatis 13 (12) , pp. 2253-2259. 10.1111/jth.13166

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Abstract

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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Dentistry
Subjects: R Medicine > RK Dentistry
Uncontrolled Keywords: Matrix Metalloproteinase 13; collagen; collagenase, platelets, GPVI collagen receptor
Publisher: Wiley-Blackwell
ISSN: 1538-7933
Funders: British Heart Foundation, Wellcome Trust, Tenovus
Date of Acceptance: 23 September 2015
Last Modified: 16 Jan 2019 14:44
URI: http://orca.cf.ac.uk/id/eprint/79131

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