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Thromb Haemost 2014; 111(06): 1089-1101
DOI: 10.1160/TH13-07-0588
Cardiovascular Biology and Cell Signalling
Schattauer GmbH

Matrix metalloproteinase-2 of human carotid atherosclerotic plaques promotes platelet activation

Correlation with ischaemic events
Massimo Lenti
1   Division of Vascular and Endovascular Surgery, Hospital S. M. Misericordia, Perugia, Italy
,
Emanuela Falcinelli
2   Department of Internal Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy
,
Marcella Pompili
2   Department of Internal Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy
,
Paola De Rango
1   Division of Vascular and Endovascular Surgery, Hospital S. M. Misericordia, Perugia, Italy
,
Valentina Conti
2   Department of Internal Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy
,
Giuseppe Guglielmini
2   Department of Internal Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy
,
Stefania Momi
2   Department of Internal Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy
,
Teresa Corazzi
2   Department of Internal Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy
,
Giuseppe Giordano
1   Division of Vascular and Endovascular Surgery, Hospital S. M. Misericordia, Perugia, Italy
,
Paolo Gresele
2   Department of Internal Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy
› Author Affiliations Financial support: This study was supported in part by a grant from Fondazione Cassa di Risparmio di Perugia (project n. 2011.0137.021) and by a gratuity from Banca d′Italia, Perugia Branch (prot 0557797/12) to P.G.
Further Information

Publication History

Received: 19 July 2013

Accepted after major revision: 21 February 2013

Publication Date:
21 November 2017 (online)

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Summary

Purified active matrix metalloproteinase-2 (MMP-2) is able to promote platelet aggregation. We aimed to assess the role of MMP-2 expressed in atherosclerotic plaques in the platelet-activating potential of human carotid plaques and its correlation with ischaemic events. Carotid plaques from 81 patients undergoing endarterectomy were tested for pro-MMP-2 and TIMP-2 content by zymography and ELISA. Plaque extracts were incubated with gel-filtered platelets from healthy volunteers for 2 minutes before the addition of a subthreshold concentration of thrombin receptor activating peptide-6 (TRAP-6) and aggregation was assessed. Moreover, platelet deposition on plaque extracts immobilised on plastic coverslips under high shear-rate flow conditions was measured. Forty-three plaque extracts (53%) potentiated platelet aggregation (+233 ± 26.8%), an effect prevented by three different specific MMP-2 inhibitors (inhibitor II, TIMP-2, moAb anti-MMP-2). The pro-MMP-2/TIMP-2 ratio of plaques potentiating platelet aggregation was significantly higher than that of plaques not potentiating it (3.67 ± 1.21 vs 1.01 ± 0.43, p<0.05). Moreover, the platelet aggregation-potentiating effect, the active-MMP-2 content and the active MMP-2/pro-MMP-2 ratio of plaque extracts were significantly higher in plaques from patients who developed a subsequent major cardiovascular event. In conclusion, atherosclerotic plaques exert a prothrombotic effect by potentiating platelet activation due to their content of MMP-2; an elevated MMP-2 activity in plaques is associated with a higher rate of subsequent ischaemic cerebrovascular events.

Keywords

Atherosclerotic plaques - biomarker - matrix metalloproteinases - platelets - TIA/stroke

 

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