Investigation by immunofluorescence of arterial lesions in rabbits on two different lipid supplements and treated with pyridinol carbamate.

Rabbits maintained on a pellet diet supplemented with cholesterol, or on a semi-synthetic diet containing beef fat but no added cholesterol, have been studied in relation to their development of hyperlipidaemia and of lipid-filled arterial lesions. The influence of pyridinol carbamate on animals on both diets was also examined but found to produce no significant effect. Animals on both diets developed a hyperlipoproteinaemia. In cholesterol-fed animals this developed quickly, became gross, and was characterized by the presence of an anomalous lipoprotein of very low density, large molecular size and abnormally high cholesterol content. Beef fat fed animals showed a more moderate hyperlipidaemia which developed more slowly and the lipoproteins qualitatively resembled those in normal rabbits. Differences in the rate and severity of development of aortic lesions between the two different dietary supplements were found to reflect differences in the duration and intensity of hyperlipoproteinaemia between the groups. Arterial lesions in cholesterol-fed animals were more extensive and contained larger numbers of fat-filled cells than those in beef fat-fed animals. Comparisons were made (in many cases on the identical section) between lesions treated with a fluorescein labelled antiserum to total rabbit serum low density lipoproteins (TLDL) and with a conventional lipid stain. Precise agreement was found between the distribution of lipid reacting with Oil red 0 and specific fluorescence for TLDL in endothelial cells, in extracellular deposits in the intimal ground-substance and in medial smooth muscle cells. But fat-filled cells in the intima and in reticulo-endothelial tissue showed variable immunofluorescent reactivity. The reason for this discrepancy is discussed. Agreement between the distribution of conventional lipid staining and specific immunofluorescence for TLDL was also found in extracellularly distributed material in arterioles and smaller vessels at certain sites. It is suggested that these results establish that rabbit TLDL serve as the vehicles transporting lipid into the experimental lesions, just as the homologous human lipoproteins do in human atherosclerosis.