Anti-atherosclerotic properties of the acyl-coenzyme A:cholesterol acyltransferase inhibitor F 12511 in casein-fed New Zealand rabbits.

The anti-atherosclerotic properties of F 12511, a novel acyl-coenzyme A:cholesterol acyltransferase (ACAT) inhibitor, were studied in rabbits that were fed a cholesterol-free casein-rich diet and developed endogenous hypercholesterolemia and fibrofatty preatheroma lesions. After 6 weeks of casein feeding, an endothelial abrasion was performed in the abdominal aorta; at week 8, a control group was maintained on this diet while F 12511 (8 mg/kg/d) was administered as a diet admixture for the subsequent 24 weeks. Total plasma cholesterol level rose to 250-300 mg/dl in both groups before starting the treatment; F 12511 time-dependently reduced total plasma cholesterol by 50%, and also decreased by 50% the incidence of lesions and macrophage accumulation in uninjured aorta (thoracic arch, celiac bifurcation).