Chemical composition and physical state of lipid deposits in atherosclerosis

Abstract

The composition, morphology, and physical properties of lipids in atherosclerotic lesions from human aortas were studied in order to elucidate the factors for the accumulation of cholesterol and its esters in the vessel wall. Lesions were classified histologically into 3 groups: fatty streak, fibrous plaque, and advanced plaque. The relative lipid composition of the lesions was plotted on the phase diagram of the 3 major lipids: cholesterol, cholesteryl ester, and phospholipid. Early fatty streaks had compositions within the 2-phase zone with a cholesterol-phospholipid liquid crystalline phase and a cholesteryl ester oily phase. Advanced fatty streaks and fibro-fatty plaques fell within the 3-phase zone with excess free cholesterol. Advanced plaques also had an average lipid composition within the 3-phase zone, but with a larger excess of free cholesterol. From the lipid-chemical point of view there is a continuous progression from early fatty streaks through advanced fatty streaks and fibro-fatty plaques to advanced plaques. In fatty streaks the cholesteryl esters accumulate in the form of isotropic and anisotropic droplets. The latter are in the smectic liquid crystalline state with the molecules arranged in layers and have surfaces that are spherical and smooth. Fibrous and advanced plaques showed beside droplets also amorphous lipids and cholesterol monohydrate crystals. Some of the amorphous lipids were solid up to about 45 degrees C and exhibited a smectic phase at cooling, indicating cholesteryl esters as the major component. The transition temperatures of high-melting cholesteryl esters, e.g. palmitate, are depressed by low-melting ones. Most of the triglycerides are present in the cholesteryl ester droplets and abolish the cholesteric liquid crystalline phase.