Chemical composition and physical state of lipid deposits in atherosclerosis.

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.

[1]  B. Lundberg,et al.  Accumulation and mobilization of cholesteryl esters in cultured human fibroblasts exposed to free cholesterol-rich phospholipid vesicles. , 1985, Atherosclerosis.

[2]  E. B. Smith,et al.  The lipids in raised fatty and fibrous lesions in human aorta. A comparison of the changes at different stages of development. , 1968, Journal of atherosclerosis research.

[3]  G. R. Bartlett.  Phosphorus assay in column chromatography. , 1959, The Journal of biological chemistry.

[4]  E. B. Smith,et al.  The microdissection of large atherosclerotic plaques to give morphologically and topographically defined fractions for analysis. 2. Studies on "nile blue" cells. , 1972, Atherosclerosis.

[5]  P. Brecher,et al.  Properties of acyl-CoA:cholesterol O-acyltransferase in aortic microsomes from atherosclerotic rabbits. , 1980, Biochimica et Biophysica Acta.

[6]  S. Mathur,et al.  Role of acylcoenzyme A: cholesterol o-acyltransferase in cholesterol metabolism. , 1979, Progress in lipid research.

[7]  G. Shipley,et al.  The ternary phase diagram of lecithin, cholesteryl linolenate and water: phase behavior and structure. , 1974, Journal of molecular biology.

[8]  D. B. Zilversmit.  Mechanisms of cholesterol accumulation in the arterial wall. , 1975, The American journal of cardiology.

[9]  A. Gotto,et al.  Correlation of apolipoprotein B retention with the structure of atherosclerotic plaques from human aortas. , 1978, Laboratory investigation; a journal of technical methods and pathology.

[10]  G. Shipley,et al.  The phase behavior of hydrated cholesterol. , 1979, Journal of lipid research.

[11]  W. Insull,et al.  Lipid droplets in atherosclerotic fatty streaks of human aorta. , 1970, The Journal of clinical investigation.

[12]  B. Lundberg.  Thermal properties of systems containing cholesteryl esters and triglycerides. , 1976, Acta chemica Scandinavica. Series B: Organic chemistry and biochemistry.

[13]  J. Folch,et al.  A simple method for the isolation and purification of total lipides from animal tissues. , 1957, The Journal of biological chemistry.

[14]  L. Arbogast,et al.  Cellular cholesterol ester accumulation induced by free cholesterol-rich lipid dispersions. , 1976, Proceedings of the National Academy of Sciences of the United States of America.

[15]  O. Stein,et al.  Deposition and mobilization of cholesterol ester in cultured human skin fibroblasts. , 1976, Biochimica et biophysica acta.

[16]  S. Dayton,et al.  Studies of the mechanism of augmented synthesis of cholesteryl ester in atherosclerotic rabbit aortic microsomes. , 1977, Atherosclerosis.

[17]  W. Insull,et al.  Cholesteryl ester-rich inclusions from human aortic fatty streak and fibrous plaque lesions of atherosclerosis. I. Crystalline properties, size and internal structure. , 1974, The American journal of pathology.

[18]  G. Shipley,et al.  Physical-chemical basis of lipid deposition in atherosclerosis. , 1974, Science.

[19]  M. Brown,et al.  Lipoprotein receptors, cholesterol metabolism, and atherosclerosis. , 1975, Archives of pathology.

[20]  R. Tuckey,et al.  Methanolysis of cholesteryl esters: conditions for quantitative preparation of methyl esters. , 1979, Analytical biochemistry.

[21]  G. Shipley,et al.  Physical chemistry of the lipids of human atherosclerotic lesions. Demonstration of a lesion intermediate between fatty streaks and advanced plaques. , 1976, The Journal of clinical investigation.

[22]  D. Small.  The Physical State of Lipids of Biological Importance: Cholesteryl Esters, Cholesterol, Triglyceride , 1970 .

[23]  R. Scow,et al.  Scanning electron microscopic study of chylomicrons incubated with lipoprotein lipase , 1976, The Anatomical record.

[24]  S. Dayton,et al.  Esterification of cholesterol by homogenates of atherosclerotic and normal aortas. , 1973, Life sciences. Pt. 2: Biochemistry, general and molecular biology.

[25]  H. Kruth.  Histochemical detection of esterified cholesterol within human atherosclerotic lesions using the fluorescent probe filipin. , 1984, Atherosclerosis.

[26]  D. Engelman,et al.  Compositional mapping of cholesteryl ester droplets in the fatty streaks of human aorta. , 1976, The Journal of clinical investigation.

[27]  F. R. Smith,et al.  Cholesterol turnover in lipid phases of human atherosclerotic plaque. , 1982, Journal of lipid research.

[28]  C. W. Adams,et al.  Connective-tissue reactions to implantation of purified sterol, sterol esters, phosphoglycerides, glycerides and free fatty acids. , 1967, The Journal of pathology and bacteriology.

[29]  A. Gotto,et al.  Quantification of Apolipoprotein B in Grossly Normal Human Aorta , 1977, Circulation research.

[30]  D. Small,et al.  Isolation and and partial characterization of the lipid phases of human atherosclerotic plaques. , 1980, Journal of Biological Chemistry.

[31]  R. Shireman,et al.  Uptake of [3H]cholesterol from low density lipoprotein by cultured human fibroblasts. , 1982, Biochimica et biophysica acta.

[32]  H. Bogren,et al.  AN X-RAY-DIFFRACTION STUDY OF CRYSTALLINE CHOLESTEROL IN SOME PATHOLOGICAL DEPOSITS IN MAN. , 1963, Biochimica et biophysica acta.

[33]  J. Gaubatz,et al.  Isolation, purification, and characterization of a lipoprotein containing Apo B from the human aorta. , 1982, Atherosclerosis.

[34]  O. B. Bayliss,et al.  Crystals in atherosclerotic lesions: real or artefact? , 1975, Atherosclerosis.

[35]  C. Ashall,et al.  Low-density lipoprotein concentration in interstitial fluid from human atherosclerotic lesions. Relation to theories of endothelial damage and lipoprotein binding. , 1983, Biochimica et biophysica acta.