Xanthomatosis and atherosclerosis produced by diet in an adult rhesus monkey.

Abstract

I T HAS proved difficult to establish with certainty the relationship bet.ween diet and atherosclerosis in human subjects.‘1 * Important limitat,ions of time and ethics prevent direct feeding experiments, and the multiplicity of environmental variables present in natural situations restricts the interpretation of diet-disease observations. An alternative to this dilemma is the study of the relation of diet to atherosclerosis in subhuman, primate species. Few attempts have been made to produce atherosclerosis in rhesus monkeys. Hueper found no evident disease in young rhesus monkeys that were fed diets containing cholesterol for periods of 8 to 16 months. Rinehart and Greenberg4, 5 have described nonfatty changes in the vessels of pyridoxine-deficient rhesus monkeys which they consider equivalent to those of human arteriosclerosis. Experiments with 12 cebus and 3 rhesus monkeys in this laboratory6 have not reproduced these findings. Recently Mushett and Emersonfia have confirmed the work of Rinehart and Greenberg in rhesus monkeys and dogs. It has been shown in this laboratory with the New World cebus monkey that vascular disease resembling human atherosclerosis can be readily produced by the concurrent presence of a mild deficiency of organic sulfur compounds and a large cholesterol intake.? This disease is preceded by significant increases of both serum cholesterol and beta-lipoprot,ein levels. The increases of the latter are restricted to the &O-40 classes (media density = 1.063)) and the blood serum remains clear. The procedure does not lead to gross visceral or cutaneous cholesterolosis. While cebus monkeys regularly show limbal deposits resembling the so-called arcus senilis seen in some human subjects, these deposits are not increased with age or by the atherogenic treatment described. The clinical evidence strongly supports a relationship between xanthomatosis and premature atherosclerosis in human subjects.” Xanthomatosis appears to be one manifestation of a Mendelian trait which is more regularly characterizcd by the presence of hypercholesteremia.8 Studies done in collaboration with 1118. Edwin Wheeler have established that the serum lipid abnormality o-f xanthoma-