Injury to the arterial endothelium and foam cell formation are key initial events in the development of atherosclerosis. Although diets have been demonstrated to have an influence on the risk of the development of atherosclerosis, the dietary factors that promote the injury of the endothelium and foam cell formation are not well understood. Extreme dietary manipulation in experimental animals has been shown to promote injury of arterial endothelium, and to produce variant lipoproteins which can induce foam cell formation in cultured macrophages. Moderate modifications of diets in humans have been shown to cause changes in both the level and chemical composition of lipoproteins in plasma, but it is not clear if such changes accompany the change in potencies of lipoproteins to promote the injury of endothelium and foam cell formation in humans. Numerous long term diet studies in humans have shown that the intake of a diet containing high level of animal (saturated) fat increases the level of serum cholesterol, while the intake of diet containing a high level of vegetable (polyunsaturated) fat lowers serum chlesterol. Thus, it is generally believed that saturated fat is more atherogenic than unsaturated fat although there is no direct experimental evidence at the cellular level. Dietary fat and cholesterol are exclusive precursors of postprandial lipoproteins but do not directly enter into the formation of lipoproteins (VLDL and LDL) in fasting blood. The main objective of this proposal is to determine atherogenic potencies of postprandial lipoproteins appearing in blood shortly after an ingesting a fatty meal containing a high level of animal or vegetable fat. Atherogenic potencies will be assessed by a model system of early atherosclerosis which measure the endothelial barrier function and the foam cell formation induced by postprandial lipoproteins.
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