Rosuvastatin Therapy Does Not Affect Serum MMP-13 or TIMP-1 Levels in Hypercholesterolemic Patients.

摘要

Matrix metalloproteinases degrade the collagen content of atherosclerotic plaque and reduce plaque stability. In tissue sections of atherosclerotic plaque, the expression of matrix metalloproteinases is increased. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) decrease the tissue expression of matrix metalloproteinases-1, -2, -3, and -9 in atheromatous plaque by attenuating the inflammatory process that leads to increased expression. However, it is not known whether statins decrease levels of matrix metalloproteinase-13-an enzyme crucial to the initiation of collagen degradation-as part of their plaque-stabilizing effect.We prospectively examined the effect of statin therapy on serum levels of matrix metalloproteinase-13, tissue inhibitor of metalloproteinase-1, and low-density-lipoprotein cholesterol in 14 patients with hypercholesterolemia. All were at low risk for adverse cardiovascular events and were given 20 mg/d of rosuvastatin for 4 weeks. Post-therapy levels of matrix metalloproteinase-13 and tissue inhibitor of metalloproteinase-1 were compared with baseline levels. Although low-density-lipoprotein cholesterol levels were significantly decreased in the 14 patients (mean baseline level, 152 +/- 21 mg/dL vs mean post-therapy level, 73 +/- 45 mg/dL; P < 0.001), matrix metalloproteinase-13 and tissue inhibitor of metalloproteinase-1 levels were unchanged (matrix metalloproteinase-13, 0.295 +/- 0.06 ng/mL vs 0.323 +/- 0.11 ng/mL, P = 0.12; and tissue inhibitor of metalloproteinase-1, 400.8 +/- 43.4 ng/mL vs 395.3 +/- 47.5 ng/mL, P = 0.26). We conclude that even though there was a decrease in low-density-lipoprotein cholesterol, short-term, high-dose rosuvastatin therapy has no effect on matrix metalloproteinase-13 and tissue inhibitor of metalloproteinase-1 levels in hypercholesterolemic patients. However, further investigation is warranted.