Paraoxonase-1 arylesterase activity is an independent predictor of myeloperoxidase levels in overweight patients with or without cardiovascular complications.

ABSTRACT

OBJECTIVES: Myeloperoxidase (MPO), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were shown to contribute to atherogenesis, while human paraoxonase-1 (PON1) protects against oxidative stress. Although several studies investigated these biomarkers, their associations have not been completely clarified yet. We aimed to investigate these parameters in overweight hyperlipidemic, lipid-lowering therapy-naive patients (n=167) with and without vascular complications. DESIGN AND METHODS: MPO, MMP-9 and TIMP-1 levels were measured by ELISA. PON1 activities were detected spectrophotometrically. PON1 phenotype was calculated by using a dual substrate method. RESULTS: Patients with vascular complications (VC) had significantly higher MPO and TIMP-1 levels compared to those without (patients with no vascular complications; NVC) (728 (367.25-1177.90) mg/ml vs. 315.9 (176.05-687.40) mg/ml; p<0.001; and 172.7 (157.7-197.7) ng/ml vs. 152.6 (129.3-172.3) ng/ml; p<0.0001; respectively). MPO levels showed a significant negative correlation with PON1 arylesterase activity (whole patient group (W) r=0.42, p<0.0001; VC r=0.44, p=0.01; NVC r=0.39, p<0.0001) and positive correlations with MMP-9 (W r=0.37, p<0.0001; VC r=0.29, p=0.07; NVC r=0.42, p<0.0001) and TIMP-1 (W r=0.42, p<0.0001; VC r=0.33, p<0.05; NVC r=0.41, p<0.0001), respectively. PON1 arylesterase activity was found to be an independent predictor of MPO levels in the whole patient group (ß=-0.350, p<0.0001) or when studied separately in the subgroups with or without cardiovascular complications (VC ß=-0.57, p<0.05; NVC ß=-0.33, p<0.0001). CONCLUSIONS: Our results suggest that parallel investigation of MPO, MMP-9 and TIMP-1 levels and PON1 arylesterase activity may be a more accurate indicator of atherosclerosis, which may allow earlier treatment and therefore, improvement of treatment efficacy.