Reversal of advanced atherosclerosis in Rhesus monkeys: Part 1. Light-microscopic studies

Abstract

The regression of atherosclerotic lesions in Rhesus monkeys was evaluated by means of a low-fat, low-cholesterol diet with or without N-γ-phenylpropyl-N-benzyloxy acetamide (W-1372). Moderate to severe aortic and coronary atherosclerosis was induced by feeding 4 groups of male monkeys a high-fat, high-cholesterol diet for 18 months, after which the first group was autopsied for assessment of the lesions. During a subsequent 18-month regression period, the second group of animals was fed a low-fat, low-cholesterol diet with W-1372, and the third group the low-fat, low-cholesterol diet without W-1372. A pair of monkeys (the fourth “group”) was fed an atherogenic diet throughout the experiment. Serum cholesterol, which increased about 5-fold during the induction period, returned to baseline values or below in the 2 treated groups. Evidence of regression of lesions was obtained in both these groups, but was most noticeable in the monkeys fed the low-fat, low-cholesterol diet without W-1372. The aortas of the animals treated with the low-fat, low-cholesterol diet with or without W-1372 showed about two-thirds as many lesions which were on the average about half as severe as those in the animals killed at 18 months. The coronary artery lesions showed a similar contrast, with the treated groups having about one-third to one-half as many lesions which were about one-half to two-thirds as severe. In both locations the differences in frequency and severity of arterial lesions were statistically significant when the reference group killed at 18 months was compared with the group treated with the low-fat, low-cholesterol diet without W-1372.