Isolation and characterization of plasma lipoproteins of common marmoset monkey. Comparison of effects of control and atherogenic diets.

Abstract

This study examines the potential of the common marmoset monkey (Callithrix jacchus) to serve as a model for human lipoprotein metabolism and atherosclerosis. The lipoproteins of animals fed a low-fat, low-cholesterol diet and a high-fat (12% wt/wt lard), high-cholesterol (0.34% wt/wt) diet were characterized by the combination of sequential ultracentrifugation and Pevikon block electrophoresis. Based on chemical and physical properties, equivalents of human very low density lipoproteins (VLDL), low density lipoproteins (LDL), and high density lipoproteins (HDL), including and HDL-with apolipoprotein E subclass, were demonstrated. In control animals, whose plasma cholesterol concentration was 140.1 +/- 20.2 mg/dl (means +/- SD), approximately 40% of the plasma cholesterol was transported by LDL as compared with approximately 70% in humans. The cholesterol-fed marmosets segregated into two groups: hypo- and hyper-responders. The hyper-responders had plasma cholesterol levels of 450 to 970 mg/ml. The hypercholesterolemia was associated with elevated concentrations of VLDL, intermediate density lipoproteins, and LDL; in addition, these lipoproteins were enriched in cholesteryl esters relative to lipoproteins isolated from control animals. The HDL (d greater than 1.09 g/ml) levels did not change in response to cholesterol feeding, although the HDL-with apolipoprotein E found in the d = 1.02 to 1.09 g/ml fraction increased approximately fivefold. Based on immunological characteristics and sialic acid content, the common marmoset appeared to lack a lipoprotein(a) equivalent. The results of a short-term feeding study (11 months) suggest that this monkey was susceptible to the development of diet-induced atherosclerosis. The hyper-responsive animals developed foam cell lesions and moderately proliferative intimal lesions, predominantly within the thoracic aorta. In summary, the results of our studies indicate that the common marmoset monkey potentially is a useful model for the study of both lipoprotein metabolism and diet-induced atherosclerosis.