Gross atherosclerosis was produced in the rat by feeding purified diets containing cholesterol, sodium cholate, and thiouracil for periods up to 363 days. In a few weeks a marked increase of the serum cholesterol and beta lipoproteins as well as of the liver lipides was observed. Lesions visible in the gross were found on the intimal surfaces of the vessels of all 46 animals examined. These were most prominent in the heart valves and aortic arch. The earliest lesions, which were seen at 31 days, required Sudan staining for gross demonstration. Older lesions were visible without staining. Microscopic coronary artery lesions were present and in one instance were accompanied by massive myocardial infarction. Vascular lesions were characterized by medial and intimal lipide infiltration and cellular intimal plaque formation. In a part of this study the protein level of the diet was altered at the expense of sucrose. The hypercholesteremic response among the rats varied according to the dietary protein level. The lowest response was observed among those animals receiving the highest level of dietary protein. A difference, however, in the severity and extent of the arterial lesions among these relatively small groups of rats could not be established under these experimental conditions. In all these experiments a close correlation existed between the serum cholesterol levels and beta lipoproteins of the Sf20–100 range.

Atherosclerosis has been produced in Cebus monkeys by dietary means. This disease has been produced by feeding diets high in cholesterol and low in sulfur amino acids over periods of 18 to 30 weeks. Within 2 to 8 weeks this regimen caused the concentration of cholesterol in the serum to rise to 300 to 800 mg. per cent. The hypercholesterolemia could be largely prevented by feeding 1 gm. per day of dl-methionine or l-cystine as supplements to the diet. After the serum concentration had become elevated, it could be restored to normal by feeding 1 gm. of dl-methionine but only partially restored by 0.5 gm. of l-cystine daily. The vascular lesions were in the ascending aorta but extended from the valves of the left ventricle to the proximal portions of the carotid and femoral arteries. Minimal lesions have been observed in the coronary arteries. The aortic lesions were chiefly characterized by the presence of lipid-laden phagocytes and increase in collagen and elastic fibers. The lipids were in part cholesterol derivatives. Visceral cholesterolosis was not associated with this disease.

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