Simvastatin inhibits myointimal hyperplasia following carotid artery injury in cholesterol-fed rabbits.
The effect of simvastatin, a potent inhibitor of 3-hydroxy 3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) was evaluated in an experimental model of myointimal hyperplasia in cholesterol-fed rabbits. Myointimal hyperplasia was induced by an air-drying injury of the left carotid artery followed by a 2%-cholesterol diet for 14 days. A 2-week oral treatment with simvastatin (6 mg/kg/day, p.o.) significantly lowered the circulating levels of cholesterol and triglycerides (41% and 49% inhibition respectively) as well as the low density lipoprotein (LDL)-cholesterol and high density lipoprotein (HDL)-cholesterol levels. Simvastatin also strongly affected the uptake of cholesterol in the arteries occurring as a consequence of vascular injury (44% inhibition, P < 0.001). Morphometric analysis revealed that both the intima and the media areas increased substantially 2 weeks after the lesion and showed a considerable smooth muscle cell accumulation in the neointima together with the presence of numerous foam cells. A 16-day oral treatment with simvastatin strongly reduced smooth muscle cells hyperplasia occurring in both the media and the intima following deendothelialization (19% and 60% inhibition respectively) suggesting that simvastatin may be a useful inhibitor of restenosis which occurs following vascular injury.
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Sanofi Recherche, Haemobiology Research Department, Toulouse, France.
Mares
A
A
Herbert
J
J
D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D004036:Diet, Atherogenic; D006965:Hyperplasia; D008148:Lovastatin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011817:Rabbits; D019821:Simvastatin; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology
D000924:Anticholesteremic Agents; D002791:Cholesterol, Dietary; D008148:Lovastatin; D019821:Simvastatin