MMP and TIMP alterations in asymptomatic and symptomatic severe recurrent carotid artery stenosis

Abstract

Objectives: This study aimed to determine whether the plasma levels of matrix metalloproteinases (MMPs)-2 and -9 and their specific inhibitors (tissue inhibitors of metalloproteinases (TIMPs-1 and -2)) were altered in patients with symptomatic and asymptomatic, severe, recurrent carotid artery stenosis.

Patients: Fifty-two patients (out of a total of 621) who had undergone successful carotid artery endarterectomy (CEA) between 1999 and 2003 and developed recurrent carotid artery stenosis (>/=70%) were included in the study. Restenosis was symptomatic in 23 patients and asymptomatic in 29 patients.

Methods: Recurrent carotid artery stenosis was classified based on presentation, and as early-intermediate (6 months to 3 years) or late (>3 years). A detailed clinical history was taken and two blood samples were drawn from each patient to determine plasma levels of MMPs and TIMPs along with other biological parameters. Recurrent stenosis was confirmed with computed tomographic angiography.

Results: Patients with symptomatic restenosis had significantly (p<0.001) higher active MMP-2 and -9 plasma values and significantly (p<0.001) lower TIMP-1 and -2 plasma values when compared to patients with asymptomatic restenosis. Plasma concentrations of active MMPs were higher and TIMPs lower in patients affected with late recurrent stenosis as compared to early-intermediate restenosis (p<0.001). No differences were recorded in latent MMP plasma values. Multivariate analysis showed that active MMP-2 and -9 were independent predictors of late recurrent carotid artery stenosis (p<0.03 and p<0.001, respectively).

Conclusions: Higher plasma concentrations of active MMP-2 and -9 were associated with an increased risk of carotid restenosis with plaque recurrence.