Arterial metabolism of lipoproteins in relation to atherogenesis.
In this short review we have concentrated on the ways in which modification of LDL structure may account for foam cell formation. We have presented in vivo evidence as well as in vitro evidence supporting the proposition that modification of native LDL is a prerequisite for foam cell formation and atherogenesis. Actually, oxidized LDL can contribute to atherogenesis in other ways as well. Oxidized LDL is chemotactic for circulating monocytes, yet inhibits the motility of the tissue macrophage as shown by Quinn et al. Also, oxidized LDL is cytotoxic as discussed above and this could play a crucial role in the transition from the fatty streak lesion to the clinically more consequential fibrous plaque and complicated lesion. If further research supports the importance of LDL modification in atherogenesis, a whole new array of possibilities opens itself to us for intervention. Anything that interferes with the relevant modifications of the LDL structure would presumably be additive to interventions lowering the plasma concentration of LDL. At the moment, the only such intervention that appears to be feasible is prevention of LDL oxidation. Possibly we may find ways to interfere with immune mechanisms that are involved in some patients; conceivably we might be able to interfere with the aggregation of LDL with itself or with other complexes in the artery wall that appear also to favor initiation of the atherogenic process.
Steinberg
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Department of Medicine, University of California, San Diego, La Jolla 92093-0613.
D000818:Animals; D001158:Arteries / Q000378:metabolism*; D001161:Arteriosclerosis / Q000209:etiology* / Q000378:metabolism; D015815:Cell Adhesion Molecules; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000502:physiology; D009000:Monocytes / Q000502:physiology; D011973:Receptors, LDL / Q000502:physiology; D051116:Receptors, Scavenger
D015815:Cell Adhesion Molecules; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D051116:Receptors, Scavenger