HMG-CoA reductase inhibitors reduce matrix metalloproteinase-9 activity in human varicose veins.
Matrix metalloproteinases (MMPs) have been implicated in tissue degradation in varicose veins. The aim of this study was to investigate the effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) on the activity of MMPs in varicose veins. MMP-9 was present at significantly higher levels in varicose veins than in controls and was localized mainly in smooth muscle cells at the tunica media, where marked degradation of the extracellular matrix was observed. Both simvastatin and pravastatin strikingly suppressed MMP-9 activity in ex vivo culture of varicose veins. Simvastatin suppressed MMP-9 at both the mRNA and protein levels as well as at the urokinase-type plasminogen activator protein level, resulting in the dramatic suppression of MMP-9 activity induced by tumor necrosis factor-alpha. Therefore, statins suppress MMP-9 activity by multiple mechanisms in varicose veins, suggesting they may have clinical potential for the treatment of this disease.
Nomura
S
S
Department of Medical Bioregulation, Yamaguchi University School of Medicine, Ube, Japan.
Yoshimura
K
K
Akiyama
N
N
Mikamo
A
A
Furutani
A
A
Aoki
H
H
Matsuzaki
M
M
Hamano
K
K
D000368:Aged; D001483:Base Sequence; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology; D011480:Protease Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D014648:Varicose Veins / Q000188:drug therapy* / Q000201:enzymology*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9