Matrix metalloproteinase-2 of human carotid atherosclerotic plaques promotes platelet activation. Correlation with ischaemic events

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 patie...

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Bibliographic Details
Published in:	Thrombosis and haemostasis Vol. 111; no. 6; p. 1089
Main Authors:	Lenti, Massimo, Falcinelli, Emanuela, Pompili, Marcella, de Rango, Paola, Conti, Valentina, Guglielmini, Giuseppe, Momi, Stefania, Corazzi, Teresa, Giordano, Giuseppe, Gresele, Paolo
Format:	Journal Article
Language:	English
Published:	Germany 01-06-2014
Subjects:	Brain Ischemia - blood Brain Ischemia - enzymology Brain Ischemia - etiology Carotid Artery Diseases - blood Carotid Artery Diseases - complications Carotid Artery Diseases - enzymology Enzyme Precursors - physiology Gelatinases - physiology Humans Matrix Metalloproteinase 2 - physiology Matrix Metalloproteinase Inhibitors - pharmacology Models, Cardiovascular Plaque, Atherosclerotic - blood Plaque, Atherosclerotic - complications Plaque, Atherosclerotic - enzymology Platelet Activation - drug effects Platelet Activation - physiology Platelet Aggregation - physiology Tissue Inhibitor of Metalloproteinase-2 - physiology TIA/stroke biomarker matrix metalloproteinases platelets Atherosclerotic plaques
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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.
ISSN:	0340-6245
DOI:	10.1160/TH13-07-0588