Abstract
The hypothesis that oxidative modification of low density lipoprotein (LDL) might be a critically important step in atherogenesis grew out of the recognition that cholesterol accumulation in foam cells could not be due to uptake of native LDL by way of the LDL receptor. First of all, patients who totally lack LDL receptors nevertheless develop foam cell-rich lesions much like the lesions in hypercholesterolemic subjects with normal LDL receptors [1]. Second, neither cultured monocyte/macrophages [2] nor cultured smooth muscle cells [3] can be forced to accumulate any appreciable amounts of cholesterol ester by incubation with even very high concentrations of native LDL. This led to a search for alternative forms of LDL and alternative lipoprotein receptors. Chemically acetylated LDL (AcLDL) was the first modified form demonstrated to be taken up sufficiently rapidly by monocyte/macrophages to lead to cholesterol accumulation [2]. The uptake occurred by way of a new receptor, the AcLDL receptor, quite distinct from the native LDL receptor. Unlike the native LDL receptor, the acetyl LDL receptor does not downregulate as the cell cholesterol content increases, which allows the progressive accumulation of sterol. However, there is no evidence for generation of AcLDL in vivo. Oxidized LDL (OxLDL) was shown to be an alternative ligand for the AcLDL receptor and to cause accumulation of cholesterol esters in monocyte/macrophages [4]. Over the past decade a large body of evidence has accumulated demonstrating that oxidation of LDL does indeed take place in vivo and that this process may be playing a significant role in atherogenesis, at least in animal models [5,6]. If this hypothesis is valid with respect to the human disease, it would have important implications for intervention to slow the progression of atherosclerosis. Consequently there has been intense interest in the oxidation of LDL and the factors that contribute to it.
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Steinberg, D. (1998). Oxidative Modification of LDL and Atherogenesis. In: Gotto, A.M., Lenfant, C., Paoletti, R., Catapano, A.L., Jackson, A.S. (eds) Multiple Risk Factors in Cardiovascular Disease. Medical Science Symposia Series, vol 12. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-5022-4_16
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DOI: https://doi.org/10.1007/978-94-011-5022-4_16
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