Abstract 426: Epidermal Growth Factor Receptor Increases MMP-9 Expression in Carotid Plaques of Symptomatic Patients with Carotid Stenosis

Abstract

Unstable carotid atherosclerotic plaques are characterized by rupture of their fibrous cap, leading to thromboembolism and stroke. The role of MMPs in plaque disruption is not well understood. The control of MMP transcription is complex but recently, EGFR expression has been implicated in the up-regulation of MMP-9. The aim of this study was to determine the MMP-9 mRNA expression as well as other MMPs (MMP-3, -7, and -14/MT1-MMP) expression in carotid plaques as well as in isolated SMCs from asymptomatic and symptomatic patients with carotid stenosis. The MMP-2 and MMP-9 activities were determined by gelatin zymography. The mRNA transcripts of MMP-9, -3, -7, -14 and EGFR were quantified by qPCR. The activity of MMP-9 on gelatin zymograms and the MMP-9 mRNA transcripts were significantly increased in symptomatic carotid plaques and isolated SMCs compared to those from plaques of asymptomatic patients. There was a parallel increase in the mRNA transcripts of MMP-7, -3 and -14. The mRNA transcripts for EGFR were also up-regulated. These results suggest that MMP-9 may be activated by MMP-7 and -3 and thus destabilizes the symptomatic plaques of patients compared to those from asymptomatic plaques and this effect may be mediated by EGFR.