title: Rosuvastatin therapy does not affect serum MMP-13 or TIMP-1 levels in hypercholesterolemic patients.
abstract: 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.
authors: Department of Adult Cardiology, Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas 77030, USA.
authors: Cihan
authors: C
authors: Cevik
authors: Kenneth
authors: K
authors: Nugent
authors: Gary
authors: G
authors: Meyerrose
authors: Mohammad
authors: M
authors: Otahbachi
authors: Cemil
authors: C
authors: Izgi
authors: Mark
authors: M
authors: Lyte
authors: R David
authors: RD
authors: Fish
mesh_terms: D000328:Adult; D000368:Aged; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D005464:Fluorobenzenes / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000097:blood*; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D011743:Pyrimidines / Q000627:therapeutic use*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000627:therapeutic use*; D013781:Texas; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D016896:Treatment Outcome
chemical_list: D008078:Cholesterol, LDL; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D019715:Tissue Inhibitor of Metalloproteinase-1; D000068718:Rosuvastatin Calcium; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13