Evaluation of serum matrix metalloproteinases as biomarkers for detection of neurological symptoms in carotid artery disease.
OBJECTIVE: Relevant soluble matrix metalloproteinases (MMPs), their inhibitors, tissue inhibitor of metalloproteinases (TIMPs), and serological factors were analyzed as possible biomarkers for neurological symptoms in patients with carotid artery stenosis. METHODS AND RESULTS: Asymptomatic (n = 76) and symptomatic (n = 69) patients were evaluated. Serum levels of collagenases (MMP-1, -8), gelatinases (MMP-2, -9), stromelysin (MMP-3), matrilysin (MMP-7), and TIMP-1, -2 were determined by enzyme-linked immunosorbant assay (ELISA). Furthermore, fibrinogen, C-reactive protein (CRP), leukocytes, and further serological parameters were measured. Circulating MMP-7, -8, -9, and TIMP-1 were significantly enhanced in symptomatic individuals with P< .001 for MMP-7 and P< .05 for MMP-8, -9, and TIMP-1. Significant correlations were found between various MMPs with highest correlation coefficient of r = .749 between MMP-8 and -9. In addition, MMP-1, -3, -7, -9 correlated significantly with leukocytes, MMP-1, and TIMP-1 with thrombocytes, MMP-8 with fibrinogen, and MMP-7 with creatinine. Combination of more than one biomarker led to significantly enhanced positive predictive value (PPV) for neurological symptom compared to single MMP (MMP-7 + MMP-9: PPV = 73.1%, MMP-7 + MMP-8 + MMP-9: PPV = 73.8% vs. PPV = 62.5%; P< .001). CONCLUSIONS: Thus, using appropriate analytical approaches, we showed for the first time the possibility to use set of relevant biomarkers as predictors of neurological symptoms. Such biomarkers together with current diagnostic techniques may further contribute to recognize vulnerable lesions to define patients at risk.