Increased Matrix Metalloproteinase-9 Activity in Unstable Carotid Plaques

Abstract

Background and Purpose-Acute disruption of atherosclerotic plaques precedes the onset of clinical syndromes, and studies have implicated a role for matrix metalloproteinases (MMPs) in this process. The aim of this study was to establish the character, level, and expression of MMPs in carotid plaques and to correlate this with clinical status, cerebral embolization, and histology. Methods-Plaques were obtained from 75 consecutive patients undergoing carotid endarterectomy and divided into 4 groups according to symptomatology (group 1, asymptomatic; group 2, symptomatic Ͼ6 months before surgery; group 3, symptomatic within 1 to 6 months; group 4, symptomatic within 1 month). All patients underwent preoperative and intraoperative transcranial Doppler monitoring. Plaques were subjected to histological examination and quantification 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 4, median Ͻ32 ng/mL for all other groups; Pϭ0.003), with no difference in the levels of MMPs 1, 2, or 3. Furthermore, the MMP-9 concentration was significantly higher in plaques undergoing spontaneous embolization (Pϭ0.019) and those with histological evidence of plaque instability (PϽ0.03). 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 significantly 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. (Stroke. 2000;31:40-47.)

Association of matrix metalloproteinase-9 C1562T polymorphism and coronary artery disease: a meta-analysis

“…Indeed, MMP-9 was highly expressed in the shoulder regions of advanced atherosclerotic lesions (Galis et al, 1994;Brown et al, 1995). Its concentration and activity were significantly higher in unstable atheroseclerotic plaque with intense inflammatory cell infiltration, hence contributing to the plaque rupture ultimately (Loftus et al, 2000;Pasterkamp et al, 2000). Some cross-sectional studies have reported that the plasma MMP-9 level was significantly higher in CAD patients, in particular in acute MI, than in control subjects (Kai et al, 1998;Tayebjee et al, 2005).…”

Serum concentrations of atherogenic proteins neutrophil gelatinase-associated lipocalin and its complex with matrix metalloproteinase-9 are significantly lower in women with polycystic ovary syndrome: hint of a protective mechanism?

“…Overall, the full functional repertoire of NGAL remains to be elucidated. Of particular interest is the finding that NGAL inhibits MMP-9 inactivation, leading to enhanced proteolytic activity with prolonged effects on collagen degradation (27). Indeed, Hemdal et al have found increased expression and co-localization of MMP-9 and NGAL in atherosclerotic lesions, especially in myocardial infarction (15).…”

Evaluation of plasmatic MMP-8, MMP-9, TIMP-1 and MPO levels in obese and lean women

“…MMP-9 seems to play an important role in this process in obese individuals, as evident by its elevated plasma concentrations in these subjects [5,10,11]. In addition, clinical studies have shown that alteration in the expression or activity of MMPs and/or TIMPs is an important mechanism underlying the pathophysiology of some cardiovascular diseases [5][6][7][8] and contributes to ventricular dysfunction [6] and atherosclerotic lesions [9]. Studies evaluating circulating levels of MMP-8 (neutrophil collagenase) in obese women without associated comorbidities have not yet been evaluated, although some studies have shown higher MMP-8 levels in subjects presenting with cardiovascular disorders [12][13][14][15].…”