SUPPRESSIVE EFFECT OF SIMVASTATIN ON INTRAMURAL SMALL CORONARY ARTERIAL LESIONS IN CHOLESTEROL-FED RABBITS

The aim of this study was to examine the suppressive effect of simvast atin on intramural coronary arterial lesions in cholesterol-fed rabbit s. In one experiment, six groups of rabbits were fed laboratory chow a lone Or with added 0.1%, 0.2%, 0.3%, 0.5% or 1.0% cholesterol for 16 w eeks. In another experiment, four groups of rabbits were fed a 0.5% ch olesterol diet and treated with simvastatin at 1, 3, or 5 mg/kg/day or placebo. In each rabbit, the levels of serum total cholesterol (TC) w ere determined at 1-week intervals to calculate the integrated values. The lesion induction ratio was defined as the ratio of intramural cor onary arteries 50-150 mu m in diameter with arterial lipoidosis to the total number of arteries of the same diameter. In the two experiments , there were positive correlations between the lesion induction ratio and integrated TC (r=0.785, P<0.0001 and r=0.763, P<0.0001, respective ly). The slopes of the regression lines for integrated TC obtained in the two experiments were similar, but the lesion induction ratio in th e simvastatin-treated group was always lower, by about 14%, in compari son with that in the nonsimvastatin-treated group. These findings sugg est that simvastatin induces lesion reduction not only by reducing the levels of circulating cholesterol but also by directly suppressing th e development of lipoidosis.