Comparative primate atherosclerosis. II. A biochemical study of lipids, calcium, and collagen in atherosclerotic arteries

Abstract Arterial lipid, calcium, and collagen concentrations were determined for squirrel monkeys ( Saimiri sciureus ), African green monkeys ( Cercopithecus aethiops ), stump-tailed macaques ( Macaca arctoides ), and woolly monkeys ( Lagothrix lagothricha ) fed four types of diets with and without cholesterol for 42 mo. Comparisons were made with human arteries selected at several stages in the natural progression of atherosclerosis and the nonhuman primates were evaluated for their usefulness in the study of human atherosclerosis. Samples of normal artery, fatty streak, and plaque from the aortas of man and the nonhuman primates were fractionated by an ultracentrifugal method into a floating cholesterol layer termed “the nonbound cholesterol pool,” corresponding to the intra- and extracellular cholesterol thought to be capable of regression, and a “bound cholesterol pool” associated with the sedimenting arterial components such as membranes and connective tissue elements. The two physically distinct compartments of cholesterol were described and characterized within the atherosclerotic lesions. Most of the experimental diets fed the nonhuman primates increased the concentration of arterial lipids, especially esterified and nonesterified cholesterol. African green monkeys and stump-tailed macaques fed the atherogenic diet had greater accumulations of total cholesterol in the abdominal than thoracic aorta and were similar to man whereas squirrel monkeys were unlike man in that regard. Woolly monkeys fed the atherogenic diet had low concentrations of arterial cholesterol even though the arteries studied had intimal lesions. African green monkeys fed atherogenic diets had the most uniformly increased arterial calcium concentrations and were similar to man during the fourth and fifth decade of age as regards both arterial distribution and concentration. The stump-tailed macaques fed the atherogenic diet had 40–57% higher aortic hydroxyproline concentrations than controls indicating a very fibrous component comprising the lesion. Fatty streaks of African green monkeys, squirrel monkeys, and man had a similar concentration and distribution of total cholesterol in the lipid pools of aortic arch, thoracic aorta, and abdominal aorta; however, in that regard stump-tailed macaques were dissimilar and had low concentrations of cholesterol even though approximately 45% of the aorta was affected grossly with fatty streaks. Esterified cholesterol constituted the majority of the nonbound cholesterol pool of plaque in man and the nonhuman primates. On the basis of cholesterol distribution in atherosclerotic plaques, the stump-tailed macaque and the African green monkey seemed more similar to man. The results indicate that the African green monkey and the stump-tailed macaque would be the most useful of those species studied for investigating the lipid component of atherosclerosis. The African green monkey seems well suited for studies involving the mineral component of the lesion whereas the stump-tailed macaque appears useful for investigations on the proliferation of mesenchymal components of the artery wall and the resulting sclerogenic process.