Increased tissue factor, MMP-8, and D-dimer expression in diabetic patients with unstable advanced carotid atherosclerosis

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Authors: Jerzy Krupinski, Marta M Turu, M Angels Font, Nesser Ahmed, Matthew Sullivan, Ana Luque, Francisco Rubio, Lina Badimon, Mark Slevin

Published Date October 2007 Volume 2007:3(4) Pages 405 - 412

DOI: http://dx.doi.org/10.2147/VHRM.S

Jerzy Krupinski^1,2, Marta M Turu^1,2, M Angels Font1, Nesser Ahmed³, Matthew Sullivan³, Ana Luque^1,2, Francisco Rubio¹, Lina Badimon², Mark Slevin³

¹Department of Neurology, Stroke Unit, University Hospital of Bellvitge (HUB), Fundacio IDIBELL, Barcelona, Spain; ²Cardiovascular Research Centre, IIBB/CSIC-HSCSP-UAB, Barcelona, Spain; ³School of Biology, Chemistry and Health Science, Manchester Metropolitan University, Manchester, United Kingdom

Abstract: Advanced atherogenesis is characterized by the presence of markers of enhanced prothrombotic capacity, attenuated fibrinolysis, and by clinical conditions associated with defective coagulation. Diabetes may be associated with enhanced lesion instability and atherosclerotic plaque rupture. Plaques obtained from 206 patients undergoing carotid endarterectomy were divided into diabetic (type 2) and nondiabetic and analyzed by Western blotting and immunohistochemistry to detect tissue factor (TF), metalloproteinases (MMP)-2, -8, -9, and fibrin/fibrinogen related antigens, and in situ zymography to detect MMP activity. Plasma samples were quantified for TF procoagulant activity, C-reactive protein, fibrinogen and D-dimer. Diabetic and symptomatic patients with hypoechogenic plaques had increased plasma TF activity and D-dimer, compared with those with hyperechogenic plaques (p = 0.03, p = 0.007, respectively). Diabetic, symptomatic patients had higher plasma D-dimer levels than asymptomatic patients (p = 0.03). There was a significant correlation between intramural TF levels and D-dimer in diabetic patients with symptomatic disease (p = 0.001, r2 = 0.4). In diabetic patients, plasma fibrinogen levels were higher in patients with hypoechogenic plaques (p = 0.007). Diabetic patients with ulcerated plaques had higher plasma D-dimer and MMP-8 levels than those with fibrous plaques (p = 0.02, p = 0.01, respectively). This data suggests that currently available circulating markers may be clinically useful to select diabetic patients at higher risk of atherothrombosis. Increased procoagulant activity in diabetic patients may be linked to increased mural remodeling.

Keywords: Diabetes, atherosclerosis, carotid artery, tissue factor, D-dimer, matrix metalloproteinase.