Increased matrix metalloproteinase-9 activity in unstable carotid plaques A potential role in acute plaque disruption

Background and Purpose-Acute disruption of atherosclerotic plaques precedes the onset of clinical syndromes, and studies have implicated a role for ma trix metalloproteinases (MMPs) in this process. The aim of this study was t o establish the character, level, and expression of MMPs in carotid plaques and to correlate this with clinical status, cerebral embolization, and his tology. Methods-plaques were obtained from 75 consecutive patients undergoing carot id endarterectomy and divided into 4 groups according to symptomatology (gr oup 1, asymptomatic; group 2, symptomatic >6 months before surgery; group 3 , symptomatic within 1 to 6 months; group 4, symptomatic within 1 month), A ll patients underwent preoperative and intraoperative transcranial Doppler monitoring. Plaques were subjected to histological examination and quantifi cation of MMPs by zymography and ELISA. Results-The level of MMP-9 was significantly higher in group 4 (median 125. 7 ng/mL for group 3, median <32 ng/mL for all other groups; P=0.003), with no difference in the levels of MMPs 1, 2, or 3. Furthermore, the MMP-9 conc entration was significantly higher in plaques undergoing spontaneous emboli zation (p=0.019) and those with histological evidence of plaque instability (P<0.03). In situ hybridization demonstrated increased MMP-9 expression in highly symptomatic plaques in areas of intense inflammatory infiltrate. Conclusions-The concentration, production, and expression of MMP-9 is signi ficantly higher in unstable carotid plaques. if this proves to be a causal relationship, MMP-9 may be a strong candidate for pharmacotherapy aimed at stabilizing plaques and preventing stroke.