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The Texas Heart Journal



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Anticholesteremic agents/pharmacology, atherosclerosis/blood/drug therapy, biological markers/blood, cholesterol, LDL/blood, hydroxymethylglutaryl-CoA reductase inhibitors/pharmacology, matrix metalloproteinase 13/blood/metabolism, MMP13 protein, human, rosuvastatin/therapeutic use, tissue inhibitor of metalloproteinase-1/blood/metabolism, treatment outcome


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.



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