Lipids of human atherosclerotic plaques and xanthomas: clues to the mechanism of plaque progression

While the content of fatty streaks and fibrous plaques has been extensively studied in autopsied specimens, little is known about the lipid composition of advanced human atherosclerotic plaques requiring surgical removal. We have analyzed free cholesterol, cholesteryl ester, and the cholesteryl ester fatty acid content in 19 carotid and 7 femoral obliterative plaques obtained at endarterectomy. These were compared with values from each subject's plasma and from xanthomas removed from eight patients. The total cholesterol content was 75.1 mg/g dry weight for carotid plaques, 56.0 mg/g for femoral plaques, and 106.8 mg/g for xanthomas. The free cholesterol content was 56.6% and 50.4% of the total cholesterol for carotid and femoral plaques, respectively, while the free cholesterol of xanthomas was only 25.5%. The fatty acids of cholesteryl esters were analyzed in an attempt to identify the site of their esterification, i.e., within plasma or within plaque. This can be determined using the ratio of linoleic acid (18:2) to oleic acid (18:1) in the cholesteryl ester. The ratios were 0.36 for xanthoma, 1.62 for carotid plaque, 1.73 for femoral plaque, and 2.51 in plasma. These data emphasize two chemical changes occurring with evolution of the atherosclerotic process: 1) The cholesteryl ester fatty acid composition of the plaque becomes increasingly similar to that of plasma, and 2) there is a continuing increase in the percentage of free cholesterol. These alterations reflect a decreased metabolic efficiency within atherosclerotic lesions and may initiate events that enhance plaque progression.