Biochemical effects of moderate diet and clofibrate on swine atherosclerosis

Aortic atherosclerotic lesions were induced in swine by feeding them an atherogenic diet for 17 months. The effect of a moderate diet (up to 8 gm of cholesterol per day), with or without added clofibrate therapy, for the subsequent 12 months was assessed by biochemical analysis of carefully dissected lesions and adjacent nonlesion areas. The moderate diet alone prevented "progression," except for accumulation of free cholesterol and enhancement of total protein and collagen synthesis, and caused regression of DNA concentration to nonlesion levels. The addition of clofibrate therapy enhanced regression, with significant decreases in DNA and esterified cholesterol concentrations and in the rate of DNA synthesis. Extrapolation of these results to man suggests that a "sensible" level of dietary lipid may be prophylactic against further progression, while addition of an effective hypolipemic drug may be therapeutically useful.