Foam Cells in Explants of Atherosclerotic Rabbit Aortas Have Receptors for G-Very Low Density Lipoproteins and Modified Low Density Lipoproteins

Beta-migrating very low density lipoproteins (R-VLDL) and chemically modified low density lipoproteins (LDL), labeled with the fluorescent probe 3,3-dioctadecylindocarbocyanine (Dil), were used to determine whether foam cells from atherosclerotic lesions have lipoprotein receptors similar to those of macrophages. The advantage of the Dil probe is that it produces a brilliant fluorescence due to its retention by the cells. When cells grown from intimal-medial explants of atherosclerotic rabbit aortas were incubated with Dil-labeled R-VLDL, both smooth muscle cells and foam cells became fluorescent. However, when large amounts of unlabeled LDL were added to compete with the 13-VLDL for binding to the LDL receptors, Dil-labeled 13-VLDL binding to smooth muscle cells was blocked, and only the foam cells became highly fluorescent, due to the presence of specific receptors for B-VLDL on those cells. The foam cells in the explants also became fluorescent when incubated with Dil-labeled acetoacetylated (AcAc) LDL. The same fluorescently labeled foam cells avidly bound IgG-coated erythrocytes. It was possible to inhibit the binding of the Dil-labeled AcAc LDL to aortic foam cells by the addition of fucoidin, a known inhibitor of modified LDL binding to macrophages. Foam cells that became fluorescent were similar to cells grown from the explants that contained an abundance of Oil red 0 positive lipid droplets and demonstrated high acid lipase activity. These results suggest that macrophages were the precursors of the foam cells derived from explants of atherosclerotic rabbit aortas. One difference we noted between these foam cells and macrophages, however, was that foam cells from the explants retained their cholesteryl esters under the same culture conditions that resulted in the loss of lipid from macrophages loaded with lipoproteins in vitro. The existence of receptors for 13-VLDL on aortic foam cells supports the contention that dietary cholesterol-induced B-VLDL may be atherogenic lipoproteins in vivo. (Arteriosclerosis 3:2-12, January/February, 1983)