Cholesteryl Ester Accumulation in Foam Cells and Extracellular Space of Atherosclerotic Lesions

Takano, Tatsuya

doi:10.5551/jat1994.1.supplemment1_s1

Cited by 4 publications

(1 citation statement)

References 17 publications

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“…There were a number of lipid droplets remaining on culture slides while nuclei and membranous structures were absent. We speculated that one possible route for the accumulation of extracellular lipids in atherosclerotic lesions may be foam cell rupture and subsequent scattering of cytosolic lipid droplets (23,40). Chao et al (41) showed that there were two types of cholesterol-containing particles in the extracellular space in atherosclerotic lesions: one type of particle was enriched with CE and the other type was enriched with FC.…”

Section: Discussionmentioning

confidence: 99%

Foam cell formation containing lipid droplets enriched with free cholesterol by hyperlipidemic serum

Mori

Itabe

Higashi

et al. 2001

Journal of Lipid Research

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A monoclonal antibody, ASH1a/256C (256C), which binds to atherosclerotic lesions in Watanabe heritable hyperlipidemic rabbit (WHHL) aorta in vivo, recognizes complex structures of phosphatidylcholine mixed with neutral lipids. In the present study, a cell culture system is described in which foam cells express 256C-positive lipid droplets. J774.1 macrophages were incubated in the presence of a small volume of WHHL serum for 24 h to produce foam cells, which were then incubated without the WHHL serum for 3 days. Oil red O-positive lipid droplets appeared on day 1, and were present in the cells during the whole incubation period. The lipid droplets in the cells were positively immunostained with antibody 256C on day 4, although they were negative on day 1. Expression of the antigenic lipid droplets was also induced by the addition of acetylated LDL or sera from patients with hyperlipidemia. When foam cells were induced by the addition of WHHL serum, cellular content of cholesteryl ester was greatly increased but then decreased to near basal levels by day 4. Concomitantly, cellular free cholesterol increased during the culture period, indicating that the cholesteryl ester changes to free cholesterol by day 4. The lipid droplets in the foam cells on day 4 were positively stained with filipin, a fluorescent probe for free cholesterol, as well as with 256C antibody, indicating that free cholesterol is enriched in antigenic lipid droplets. These observations suggest that hydrolysis and rearrangement of cellular cholesterol take place in foam cells to form complex structures of phosphatidylcholine and free cholesterol in lipid droplets. -

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Section: Discussionmentioning

confidence: 99%

Foam cell formation containing lipid droplets enriched with free cholesterol by hyperlipidemic serum

Mori

Itabe

Higashi

et al. 2001

Journal of Lipid Research

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Oxidized phospholipids as a new landmark in atherosclerosis

Itabe

1998

Progress in Lipid Research

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Presence of Phospholipid-Neutral Lipid Complex Structures in Atherosclerotic Lesions as Detected by a Novel Monoclonal Antibody

Mori

Itabe

Takatoku

et al. 1999

Journal of Biological Chemistry

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A novel monoclonal antibody (ASH1a/256C) that recognizes atherosclerotic lesions in human and Watanabe heritable hyperlipidemic (WHHL) rabbit aortae is described. When 123 I-labeled ASH1a/256C antibody is injected intravenously into WHHL rabbits, it associates specifically with fatty streaks on the aorta. The antigen recognized by the antibody is lipid, based on extraction with chloroform and methanol from WHHL rabbit tissues. The antigen, purified by high performance liquid chromatography, was shown to be phosphatidylcholine (PC), which contains unsaturated fatty acyl groups based on analyses utilizing 1 H and 13 C nuclear magnetic resonance, Fourier transfer-infrared spectrum, and mass spectrometry. The antibody did not react with other classes of phospholipids or neutral lipids when tested using an enzyme-linked immunosorbent assay. When PC was mixed with either cholesterol, cholesteryl ester, or triacylglycerol, however, the reactivity of the antibody to PC increased up to 8-fold. Homogenates of aorta tissue obtained from normal and WHHL rabbits were fractionated using sucrose density gradient ultracentrifugation in which neutral lipid droplets, cellular membranes, and proteins are separated. The phospholipid content in cellular membrane fractions from WHHL rabbits was twice as high as that of normal rabbits, and there was an enormous difference in the antigenic activity in these fractions. The content of cholesterol in the cellular membrane fraction of WHHL rabbits was approximately 50 times higher than that of normal rabbits. Addition of neutral lipids to the cellular membrane fraction of normal rabbit markedly increased the antigenic activity. Atheromatous lesions in thickened WHHL rabbit aortic intima that were rich in lipid droplets were stained positively with ASH1a/256C immunohistochemically. These results strongly suggest that PC-neutral lipid complex domains are formed in atherosclerotic lesions.

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Cholesteryl Ester Accumulation in Foam Cells and Extracellular Space of Atherosclerotic Lesions

Cited by 4 publications

References 17 publications

Foam cell formation containing lipid droplets enriched with free cholesterol by hyperlipidemic serum

Foam cell formation containing lipid droplets enriched with free cholesterol by hyperlipidemic serum

Oxidized phospholipids as a new landmark in atherosclerosis

Presence of Phospholipid-Neutral Lipid Complex Structures in Atherosclerotic Lesions as Detected by a Novel Monoclonal Antibody

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