Relationships between Composition and Cellular Uptake of Lipoproteins from Normal and Hyperlipemic Swine

Young male swine fed a high fat, 1% cholesterol diet for 6 weeks developed a hyperlipemia accompanied by alterations in the composition of the very low density, intermediate density and low density lipoproteins (VLDL, IDL, LDL). High density lipoprotein (HDL) composition remained relatively constant. In addition to compositional analysis, determination of sedimentation coefficients indicated the LDL of hyperlipemic animals was of slightly larger size. The in vitro cellular uptake of normal swine and human 125I-labeled LDL by cultured human fibroblasts was similar in time- and concentration-dependent studies. The receptor-mediated uptake of normal swine 125I-labeled LDL, as well as IDL and VLDL, was significantly greater than that of hyperlipemic swine lipoproteins. Nonspecific uptake of normal and hyperlipemic 125I-labeled LDL was similar, as determined in studies with mutant receptor-negative familial hypercholesterolemic fibroblasts. It is hypothesized that the size of the lipoprotein particle may be a determinant in cellular uptake by physically limiting the number of particles that bind to the receptor site for uptake by the cell.