Production of cholesteryl ester-rich, anisotropic inclusions by mammalian cells in culture

Rothblat, George H.; Rosen, Joel M.; Insull, William; Yau, Annie O.; Small, Donald

doi:10.1016/0014-4800(77)90059-4

Cited by 32 publications

(14 citation statements)

References 12 publications

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“…With the removal of virtually all cellular TG, the resulting differences in the physical state of lipid droplets must be due solely to CE fatty acyl composition. These data agree with the results of others, which have demonstrated that CEs containing polyunsaturated fatty acids are isotropic, while those containing saturated or monounsaturated fatty acids are anisotropic at 37Њ (19)(20)(21)(22)(26)(27)(28)(29).…”

Section: Discussionsupporting

confidence: 92%

“…The fatty acyl composition of CEs also affects the physical state, with the more unsaturated the fatty acyl chain, the lower the transition temperature from an anisotropic to an isotropic physical state (19,20,22,(26)(27)(28)(29). At body temperature (37 Њ C), when CE fatty acids are mainly unsaturated, such as n-6 or n-3 polyunsaturated fatty acids, CE is in a liquid state, and when saturated or even monounsaturated fatty acids predominate, the physical state becomes liquid-crystalline (25,(29)(30)(31)(32).…”

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confidence: 99%

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Effects of LDL enriched with different dietary fatty acids on cholesteryl ester accumulation and turnover in THP-1 macrophages

Lada

Rudel

Clair

2003

Journal of Lipid Research

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LDL enriched with either saturated, monounsaturated, n-6 polyunsaturated, or n-3 polyunsaturated fatty acids were used to study the effects of dietary fatty acids on macrophage cholesteryl ester (CE) accumulation, physical state, hydrolysis, and cholesterol efflux. Incubation of THP-1 macrophages with acetylated LDL (AcLDL) from each of the four diet groups resulted in both CE and triglyceride (TG) accumulation, in addition to alterations of cellular CE, TG, and phospholipid fatty acyl compositions reflective of the individual LDLs. Incubation with monounsaturated LDL resulted in significantly higher total and CE accumulation when compared with the other groups. After TG depletion, intracellular anisotropic lipid droplets were visible in all four groups, with 71% of the cells incubated with monounsaturated AcLDL containing anisotropic lipid droplets, compared with 30% of cells incubated with n-3 AcLDL. These physical state differences translated into higher rates of both CE hydrolysis and cholesterol efflux in the n-3 group. These data suggest that monounsaturated fatty acids may enhance atherosclerosis by increasing both cholesterol delivery to macrophage foam cells and the percentage of anisotropic lipid droplets, while n-3 PUFAs decrease atherosclerosis by creating more fluid cellular CE droplets that accelerate the rate of CE hydrolysis and the efflux of cholesterol from the cell. The association of a high-fat, high-cholesterol diet with atherosclerosis has made dietary modification an important method for reducing cardiovascular disease risk. Both epidemiological and dietary studies have shown the benefits of replacing saturated with unsaturated fats (1-7); however, there is debate over which type of fat, monounsaturated or polyunsaturated, should replace saturated fats in the diet. Support for the benefits of a monounsaturated fat diet is based primarily on epidemiological evidence from such studies as the Seven Countries study (1) and the possible positive effect a monounsaturated fat diet has on the plasma lipid profile (8-11). These studies demonstrated that replacing saturated fats with monounsaturated fats lowers LDL concentrations, whereas substituting polyunsaturated for saturated fats lowers both LDL and HDL concentrations.The use of animal models has provided valuable insight into this debate through the generation of more definitive endpoints than would be possible in human studies. In studies with both African green monkeys and transgenic mice, despite the positive effects of monounsaturated fats on the plasma lipid profile, monounsaturated-fat fed animals developed similar levels of atherosclerosis as saturated fat-fed animals, while animals fed polyunsaturated fats developed less atherosclerosis (12, 13). These studies concluded that the monounsaturated-fat diet resulted in the production of a more atherogenic LDL particle, and that the atherogenicity of the LDL particle may be more important than absolute LDL and HDL concentrations (12,13).To better understand the mechanism underlyi...

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Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 99%

Effects of LDL enriched with different dietary fatty acids on cholesteryl ester accumulation and turnover in THP-1 macrophages

Lada

Rudel

Clair

2003

Journal of Lipid Research

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“…The physical state of cellular lipids was assessed by observation under polarizing light microscopy. 35 For statistical analyses of the data, significance was determined by Student's /test. 36 Replicate dishes for each treatment were analyzed by two different methods: an isopropanol extraction of cell monolayer lipids as modified from the method of McCloskey et al, 18 and a detergent solubilization method.…”

Section: Analytic Methodsmentioning

confidence: 99%

Influence of high density lipoprotein on esterified cholesterol stores in macrophages and hepatoma cells.

et al. 1990

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The clearance of this intra-cellular cholesteryl ester is central to the process of regression of an atherosclerotic lesion. It is generally accepted that clearance of this ester is dependent on its hydrolysis to free cholesterol, with release of that cholesterol to an appropriate exogenous acceptor, and high density lipoprotein (HDL), or a specific subclass of HDL, is thought to mediate this clearance process. 3 Although there is an extensive literature on the efflux of free cholesterol from cells, 4 much less emphasis has been placed on the clearance of esterified cholesterol. In a number of tissue culture systems, it has been demonstrated that cholesteryl esters are turned over via the cholesteryl ester cycie, 5 -8 a continual cycle of hydrolysis and re-esterification that can be interrupted by providing an extracellular free cholesterol acceptor that diverts free cholesterol from the cell. The ability of HDL to

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“…Given the prevalence of modifying factors in the extracellular regions, it is highly probable that in late-stage lesions very little LDL remains in its native state. Moreover, cholesterol esters associated with phospholipids, such as those found in the extracellular spaces of lesions, also produce cholesterol accumulation in macrophages [14–16]. In addition to retained lipids, in late-stage lesions, the death of foam cells also contributes to the extracellular lipid pool [17].…”

Section: Normal Cellular Lipoprotein Cholesterol Metabolismmentioning

confidence: 99%

Lysosomes, cholesterol and atherosclerosis

Jerome¹

2010

Clinical Lipidology

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Cholesterol-engorged macrophage foam cells are a critical component of the atherosclerotic lesion. Reducing the sterol deposits in lesions reduces clinical events. Sterol accumulations within lysosomes have proven to be particularly hard to mobilize out of foam cells. Moreover, excess sterol accumulation in lysosomes has untoward effects, including a complete disruption of lysosome function. Recently, we demonstrated that treatment of sterol-engorged macrophages in culture with triglyceride-containing particles can reverse many of the effects of cholesterol on lysosomes and dramatically reduce the sterol burden in these cells. This article describes what is known about lysosomal sterol engorgement, discusses the possible mechanisms by which triglyceride could produce its effects, and evaluates the possible positive and negative effects of reducing the lysosomal cholesterol levels in foam cells.

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Production of cholesteryl ester-rich, anisotropic inclusions by mammalian cells in culture

Cited by 32 publications

References 12 publications

Effects of LDL enriched with different dietary fatty acids on cholesteryl ester accumulation and turnover in THP-1 macrophages

Effects of LDL enriched with different dietary fatty acids on cholesteryl ester accumulation and turnover in THP-1 macrophages

Influence of high density lipoprotein on esterified cholesterol stores in macrophages and hepatoma cells.

Lysosomes, cholesterol and atherosclerosis

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