The Impact of Type 2 Diabetes and Atorvastatin Treatment on Serum Levels of MMP-7 and MMP-8

Aim: Novel members of matrix metalloproteinases (MMPs), MMP-7 and MMP-8, have emerged as predictors of cardiovascular events. Our study aimed to evaluate serum MMP-7 and MMP-8 concentrations in patients with type 2 diabetes mellitus (T2DM) and the effects of atorvastatin on them. Methods: We enrolled 85 statin-free subjects with concomitant T2DM and hypercholestero-lemia, but without overt micro-/macro-vascular complications (diabetic group -DG). 42 age-and gender-matched healthy subjects without chronic diseases or therapy served as healthy group (HG). All diabetic patients received fix dose of atorvastatin (20 mg/day). Clinical and anthropometrical parameters, lipids, fasting plasma glucose (FPG), serum MMP-7, MMP-8, their inhibitor (TIMP-1), IL-18, hsCRP and insulin resistance (HOMA-IR) were assayed at baseline in all participants and after 3 months in the DG. Results: At baseline, DG showed higher levels of BMI, systolic blood pressure, insulin resistance and FPG compared to HG (p < 0.05). Similarly, DG appeared with elevated concentrations of MMP-7 (4.28 +/- 1.01 ng/ml vs 2.63 +/- 1.11 ng/ml, p < 0.001), MMP-8 (73.07 +/- 21.96 ng/ml vs. 21.27 +/- 10.49 ng/ml, p < 0.001) and inflammatory markers (WBC, hsCRP, IL-18, p < 0.010). Importantly, atorvastatin treatment improved lipid profile, significantly reduced the concentrations of MMP-7, MMP-8 and inflammatory markers (p < 0.01). Moreover, there was considerable suppression of both MMP-7/TIMP-1 and MMP-8/TIMP-1 ratios (p < 0.01). In standard multiple regression analysis, the atorvastatin-induced reduction in MMP-7 was independently associated with LDL and IL-18 downregulation (R-2 = 0.648, p = 0.017). Similarly, IL-18 changes emerged as an independent determinant of MMP-8 alterations (R-2 = 0.678, p = 0.007). Conclusions: Hypercholesterolemic patients with T2DM showed elevated MMP-7 and MMP-8 serum concentrations. Atorvastatin reduced the latter concentrations and their ratio with TIMP-1. Those effects seemed mediated by the atorvastatin-induced suppression of inflammatory mediators.