title: Comparative effects of diet and statin on NO bioactivity and matrix metalloproteinases in hypercholesterolemic patients with coronary artery disease.
abstract: OBJECTIVE
  We investigated the effects of statin compared with the American Heart Association (AHA) Step I Diet on lipoproteins, vasomotor function, tumor necrosis factor (TNF)-alpha, and serological markers of plaque stability. Furthermore, we investigated the mechanism of regulation suggested by experimental studies.
  
  
  RESULTS
  For 14 weeks, we administered AHA diet+placebo and AHA diet+simvastatin (20 mg daily) to 31 and 32 randomly selected patients with coronary artery disease, respectively. Compared with diet alone, simvastatin significantly improved the percent flow-mediated dilator response to hyperemia from 3.37+/-2.28% to 5.89+/-2.35% (P<0.001) and lowered plasma levels of C-reactive protein from 0.48 to 0.10 mg/dL (P<0.001), TNF-alpha from 3.38 to 2.79 pg/mL (P<0.001), total matrix metalloproteinase (MMP)-9 from 36 to 28 ng/mL (P=0.006), and tissue inhibitor of matrix metalloproteinase-1 from 80+/-30 to 74+/-23 ng/mL (P=0.041), and simvastatin lowered to a greater extent MMP-9 activity (from 71 to 52 ng/mL, P=0.006) and MMP-9 activity/tissue inhibitor of matrix metalloproteinase-1 ratios (P=0.018), although this difference did not reach statistical significance. There were significant correlations between the degree of changes in TNF-alpha and the degree of changes in MMP-9 activity (r=0.424, P=0.016). However, no significant correlations between lipoprotein levels or flow-mediated dilation percentages and levels of plaque stability markers were determined (-0.208< or =r< or =0.243).
  
  
  CONCLUSIONS
  Simvastatin reduced serological markers of inflammation and plaque stability, independent of lipoprotein changes.
authors.affiliation: Department of Cardiology, Gachon Medical School, Incheon, Korea. kwangk@ghil.com
authors.forename: Kwang Kon
authors.initials: KK
authors.lastname: Koh
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Son
authors.forename: Jeong Yeal
authors.initials: JY
authors.lastname: Ahn
authors.forename: Dong Kyu
authors.initials: DK
authors.lastname: Jin
authors.forename: Hyung Sik
authors.initials: HS
authors.lastname: Kim
authors.forename: Yu Mi
authors.initials: YM
authors.lastname: Choi
authors.forename: Dae Sung
authors.initials: DS
authors.lastname: Kim
authors.forename: Euy-Myoung
authors.initials: EM
authors.lastname: Jeong
authors.forename: Gi Soo
authors.initials: GS
authors.lastname: Park
authors.forename: In Suck
authors.initials: IS
authors.lastname: Choi
authors.forename: Eak Kyun
authors.initials: EK
authors.lastname: Shin
mesh_terms: D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D003324:Coronary Artery Disease / Q000178:diet therapy / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D004032:Diet; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000178:diet therapy / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D007249:Inflammation / Q000097:blood / Q000178:diet therapy / Q000188:drug therapy; D008055:Lipids / Q000097:blood; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism* / Q000502:physiology; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism* / Q000502:physiology; D011446:Prospective Studies; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use; D016037:Single-Blind Method; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014666:Vasomotor System / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D002097:C-Reactive Protein; D019821:Simvastatin; D020782:Matrix Metalloproteinases