INHIBITORY EFFECT OF FLUVASTATIN AT DOSES INSUFFICIENT TO LOWER SERUM-LIPIDS ON THE CATHETER-INDUCED THICKENING OF INTIMA IN RABBIT FEMORAL-ARTERY

The anti-atherosclerotic effect of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors at doses insufficient to lower serum cholesterol was investigated in rabbit femoral artery denuded by ball oon catheter. Fluvastatin and pravastatin were given orally at doses o f 4 and 8 mg/kg per day, respectively, or 2 weeks after the catheteriz ation. There was little change in serum cholesterol, triglyceride and phospholipid by chronic treatment with the drugs. The cross-sectional area of the intima, expressed as relative values to media (I/M ratio), was increased by the catheterization, showing intimal thickening in t he denuded arteries. The I/M ratio was reduced by fluvastatin but not pravastatin; 0.327 +/- 0.060 for control, 0.116 +/- 0.035 for 4 mg/kg fluvastatin, 0.088 +/- 0.027 for 8 mg/kg fluvastatin and 0.22 +/- 0.06 9 for 8 mg/kg pravastatin. Fluvastatin (8 mg/kg)-induced effect on the I/M ratio, was prevented by the combined administration with 40 mg/kg per day mevalonate, a metabolite in the HMG-CoA reductase pathway. Th ese results suggest that fluvastatin inhibits intimal thickening after catheterization-induced injury through percutaneous transluminal coro nary angioplasty (PTCA) and that the inhibition is presumably attribut ed to reduced migration and proliferation of smooth muscle cells but n ot secondarily to a lowering of serum lipid.