An increase in size of low density lipoproteins (LDL) of African green monkeys fed saturated fat and cholesterol is associated with: 1) an enrichment in the number of saturated and monounsaturated cholesteryl esters (CE) per LDL particle, 2) an increase in the melting temperature of the LDL CE, such that, the LDL particle core is in a liquid crystalline physical state at body temperature and 3) an increase in severity of coronary artery atherosclerosis. These responses can be modified by feeding polyunsaturated (Omega-6) fat which results in smaller LDL, relative to saturated fat, that are relatively enriched in cholesteryl linoleate and have lower core melting temperatures and these animals have less atherosclerosis development. We hypothesize that the physical state of the LDL core may be an important atherogenic property of the LDL and that LDL particles with ordered cores of CE are more atherogenic than those with liquid (melted) cores because of an increased affinity of these particles for arterial proteoglycans (PG) or cellular lipoprotein receptors that may lead to increased accumulation of cholesterol in the artery wall. To test our hypothesis African green monkeys will be fed control diets containing 0.2 mg of cholesterol/Kcal or test diets containing 0.8 mg of cholesterol/Kcal with 40% of calories as lard (saturated group), oleic-acid rich safflower oil (monounsaturated) or fish oil (Omega-3 polyunsaturated). Control (n=6) or test (n=12) animals will be rotated through each of the three dietary fat regimen so that every animal serves as his own control within a given level of dietary cholesterol. These diets will be used because (1) LDL with a wide range of sizes and transition temperatures will occur and (2) monounsaturated fat and fish oil are currently being considered as potential therapeutic agents for reduction of total plasma cholesterol in human beings. LDL will be isolated from individual animals during each dietary regimen and chemical and physical properties of the LDL will be measured. The physical and chemical properties of the individual LDL will be compared to the binding affinity and capacity of these particles to arterial proteoglycans and cellular receptors. This approach should allow us to ascertain the relationships between the size and physical properties of LDL that influence binding affinity and capacity of LDL for arterial wall components. The experimental design should allow us to ascertain the effect of two potentially important therapeutic dietary regimes on these potentially atherogenic properties of LDL.
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