Lipoproteins containing apo B extracted from human aortas. Structure and function.
We have isolated, by anti-LDL affinity chromatography, apo B-containing lipoproteins from homogenates of atherosclerotic plaques excised from the human aorta. This fraction, called A-LP, has similarities with plasma LDL, such as having similar size and relative lipid composition, along with containing apo B. However, the fraction also contains some particles larger than LDL, it is more electronegative than LDL, the relative protein content is less than in LDL, and its apo B is highly degraded. A-LP is recognized by a high affinity binding site on mouse peritoneal macrophages (MPM), as suggested by dose-response curves of stimulation of cholesterol esterification. The interaction is inhibited by negatively-charged carbohydrates such as fucoidin, but excess A-LP did not inhibit the degradation of labeled acetyl-LDL by MPM, suggesting that the binding site recognizing A-LP may not be the scavenger receptor. Finally, stimulation of cholesterol esterification by A-LP in MPM is unregulated over a 48 hr time interval, leading to massive accumulations of cholesteryl esters and a transition of these MPM to a morphology characteristic of foam cells. It is possible that when monocytes enter the arterial intima at specific sites and become tissue macrophages, they internalize A-LP in an unregulated fashion. This, in turn, would make the monocyte-macrophage lipid-laden, and could explain the etiology of foam cells in fatty streak lesions. The modification in A-LP relative to P-LDL responsible for the enhanced recognition still needs to be elucidated.
D000818:Animals; D001011:Aorta / Q000032:analysis*; D001055:Apolipoproteins B / Q000032:analysis* / Q000302:isolation & purification; D001161:Arteriosclerosis / Q000378:metabolism*; D002788:Cholesterol Esters / Q000032:analysis; D002846:Chromatography, Affinity; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D066298:In Vitro Techniques; D008074:Lipoproteins / Q000097:blood; D008264:Macrophages / Q000378:metabolism; D051379:Mice
D001055:Apolipoproteins B; D002788:Cholesterol Esters; D008074:Lipoproteins