Inhibition of Experimental Hypercholesterolemia and Atherogenesis by 4-Amino Pteroylglutamic Acid (Aminopterin)

Abstract

Rabbits pretreated with Aminopterin (4-amino pteroylglutamic acid) for 4 weeks were fed an atherogenic diet for 8 weeks, during which Aminopterin injections also were continued. The atherogenic diet consisted of a stock diet with 3/4 per cent cholesterol added. As a result of some manipulation of the Aminopterin dosage during the period before cholesterol feeding was begun, some of the Aminopterin-treated animals lost weight from overdosage, and 7 of the original 20 died. The surviving animals upon reduction of dosage made good weight gains, comparable to the controls, during the cholesterol feeding period. When sacrificed after 8 weeks of cholesterol feeding, the control animals, 21 in number, all had grossly demonstrable 1+ to 4+ atheromatosis of the aorta. Of the 13 surviving Aminopterin-treated animals, 9 had no atheromatosis or doubtful deposits of minimal extent. Only 4 had definite atheromatosis comparable in extent to the controls. Serum cholesterol levels were 30 to 50 per cent lower in the treated animals than in the controls.