Comparison of the serum low density lipoprotein and of its apoprotein in the pig, rhesus monkey and baboon with that in man

Abstract

The principal form of the serum low density lipoprotein (LDL) in man, baboon, rhesus monkey and pig was isolated by preparative ultracentrifugation in the density interval 1.024-1.045 g/ml. The physicochemical characteristics of pig LDL most closely resembled those of man; thus, electrophoretic studies suggested that both baboon and rhesus LDL have a greater surface charge than that of their human counterpart, and electron-microscopic investigations showed baboon LDL (245 A) to be larger and rhesus LDL (205 A) smaller than those of man (217 A) and pig (228 A). In contrast, the immunological relationship between LDL from the two Old World monkeys and that of man was much closer (80-85% cross-reactivity by micro-immunoprecipitation) than that between pig and man (35% cross-reactivity). The principal difference between pig and human LDL appeared to reside in their protein and carbohydrate moieties. There was a marked resemblance between the protein moieties (apo-LDL) of LDL from the four species. The principal component of each animal apo-LDL was separated by gel-filtration chromatography and amounted to greater than 95% of the total protein; it exhibited a high molecular weight (greater than 250,000) upon SDS-polyacrylamide-gel electrophoresis and was indistinguishable from human apolipoprotein B in amino acid composition. Differences both between the apo-LDL and between the apo-B preparations from the four species, however, were detectable by immunological procedures. Such studies revealed inter-species relationships which were essentially the same as those observed between the respective native LDL preparations. The soluble apolipoproteins, present as minor components (less than 5%) of each apo-LDL, were compared by their electrophoretic mobility in polyacrylamide gel; the pattern seen in baboon and rhesus apo-LDL appeared to be most closely akin to that typical of their human counterpart. It is apparent that many characteristics typical of human serum LDL are found in those of the pig, rhesus monkey and baboon. Moreover, in view of the striking relationship existing between the immunological properties and apo-protein components of the LDL of the two Old World monkeys and that of man, these subhuman primates appear to be highly suitable as animal models for experimental atherosclerosis.