Extracellular Matrix Remodeling Factors as Markers of Carotid Artery Atherosclerosis

Abstract

Background and Objectives. The atherosclerotic plaque formation is a complex and multifactorial process. A key process underlying the formation of atherosclerotic lesion is extracellular matrix (ECM) remodeling. We chose proteins representing related aspects of ECM remodeling. In this study, we evaluated the plasma concentration and the tissue content of MMP-2 and MMP-9, osteoprotegerin (OPG), and fibronectin (FN) in atheromatous artery wall. We aimed to elucidate if the local changes have systemic reflection and to assess their clinical utility in patients with carotid atherosclerosis. Materials and Methods. 20 patients undergoing routine carotid endarterectomy and 40 healthy volunteers were enrolled in this study. MMPs activity and OPG and FN concentrations were measured in atherosclerotic plaques and nonchanged contiguous tissue after homogenization as well as in plasma from patients and reference group. The activity of MMPs was evaluated by gelatin zymography, and the concentration of OPG and FN was assessed by ELISA. Results. OPG concentration and MMP-9 activity showed differences between plaque and nonchanged tissue; OPG was higher in adjacent tissue P=0.0009, whereas MMP-9 was higher in plaque (proMMP-9 P=0.0003; MMP-9 P<0.0001). The OPG plasma concentration and both MMPs plasma activity were higher in patients (OPG P<0.001; proMMP-2 P=0.0292; and proMMP-9 P=0.0374), while FN plasma concentration was lower in patients than in the reference group P=0.0004. The ROC curves analysis showed the highest AUC for OPG (0.943) with 85.0% sensitivity and 92.1% specificity. Conclusions. The atherosclerotic plaque and the contiguous artery wall are biochemically different. OPG shows the highest potential to be a marker of advanced carotid atherosclerosis.