title: Statin prevents plaque disruption in apoE-knockout mouse model through pleiotropic effect on acute inflammation.
abstract: Although it has been demonstrated that statins stabilize atherosclerotic lesions in animal models of advanced atherosclerosis, there is little evidence to suggest that statins have a preventive effect on plaque rupture itself. In the present study, we examined the effect of fluvastatin on plaque disruption using a simple and quick method of plaque disruption in carotid artery lesions in apolipoprotein E-deficient mice. Male apolipoprotein E-deficient mice received normal chow and underwent ligation of the left common carotid artery just proximal to its bifurcation. Four weeks later, a polyethylene cuff was placed around the artery immediately proximal to the ligation site. Fluvastatin (10mg/kg per day) was given by oral gavage every day starting at 3 days before cuff placement. The administration of fluvastatin suppressed atherosclerotic plaque disruption accompanied by luminal thrombi by 31.5% compared with controls at 4 days after the cuff was placed at the ligated carotid artery. Fluvastatin administration decreased matrix metalloproteinase-9 expression, gelatinolytic activity, endothelial adhesion molecules expression and neutrophil infiltration, and increased type I collagen content in the cuffed region. In summary, fluvastatin was found to prevent plaque disruption through pleiotropic effect on acute inflammation in an animal model using apolipoprotein E-deficient mice.
authors.affiliation: Department of Geriatrics, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Kae
authors.initials: K
authors.lastname: Nakamura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sasaki
authors.forename: Xian Wu
authors.initials: XW
authors.lastname: Cheng
authors.forename: Akihisa
authors.initials: A
authors.lastname: Iguchi
authors.forename: Kohji
authors.initials: K
authors.lastname: Sato
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kuzuya
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D050197:Atherosclerosis / Q000188:drug therapy / Q000473:pathology*; D016893:Carotid Stenosis / Q000188:drug therapy / Q000473:pathology; D004195:Disease Models, Animal; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use*; D000077340:Fluvastatin; D015870:Gene Expression / Q000187:drug effects; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007211:Indoles / Q000627:therapeutic use*; D007249:Inflammation / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout
chemical_list: D001057:Apolipoproteins E; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D000077340:Fluvastatin; D020780:Matrix Metalloproteinase 9