MMP-12 and TIMP Behavior in Symptomatic and Asymptomatic Critical Carotid Artery Stenosis

Abstract

The aim of this study was to evaluate the levels of matrix metalloproteinase-12 (MMP-12) and tissue inhibitors of metalloproteinases (TIMP)-1, TIMP-2, TIMP-3, and TIMP-4 in patients with symptomatic and asymptomatic critical carotid artery stenosis (CAS). We enrolled 10 patients affected by symptomatic CAS within 12 hours from onset of stroke (S group) and 30 patients with asymptomatic CAS (CAS group); 31 patients matched for age, sex, and traditional cardiovascular risk factors were used as controls (RF group). Serum levels of MMP-12, TIMP-1, TIMP-2, TIMP-3, and TIMP-4 were assessed by Luminex. MMP-12 levels were significantly higher both in the S and CAS groups than in the RF group (P < .001). We found a significant decrease of all TIMPs in the CAS group compared with the RF group, whereas a significant increase was observed in the S group compared with the CAS group. A significant increase of TIMP-3 and TIMP-4 levels was observed in the S group compared with all other groups. MMP-12 is related to critical CAS both symptomatic and asymptomatic, being mainly released in the late stage of plaque development. Moreover, we suggest that a specific pattern of matrix degrading enzyme inhibitors arises during the early phases of stroke.