부산대학교 도서관

Background: Loss of interstitial collagen, especially type I collagen, renders atherosclerotic plaques prone to rupture. Subsequent thrombosis and embolism may cause stroke and myocardial infarction. Initiation of collagen breakdown requires interstitial collagenases, a matrix metalloproteinase (MMP) subfamily including MMP-8. The aim of this study was to quantify the level of MMP-8, the enzyme that preferentially degrades type I collagen, in carotid plaques, and to correlate this with features of plaque instability. Methods: Plaques were retrieved from 75 consecutive patients undergoing carotid endarterectomy. MMP-8 levels were quantified using ELISA. Histological plaque sections were assessed blindly for the presence of plaque rupture and immunostaining was performed for MMP-8. All patients underwent preoperative transcranial Doppler monitoring to detect spontaneous embolization. Results expressed as median MMP-8 concentration ng mL[sup -1] (IQR). Results: The plaque level of MMP-8 was significantly higher in patients with recent symptoms (symptoms <4 weeks), histological plaque rupture and spontaneous embolization (see Table). There was a significant correlation between MMP-8 and MMP-9 levels, a gelatinase known to be associated with plaque instability. Immunohistochemistry revealed staining for MMP-8 in areas of intense inflammatory infiltration. Discussion: The MMP-8 level is significantly higher in unstable plaques based on symptoms, histology and spontaneous embolization. Together with MMP-9, these enzymes have the potential to degrade all components of the extracellular matrix upon which plaque integrity depends, and represent a target for pharmacotherapy to prevent stroke. [ABSTRACT FROM AUTHOR]