Relationships Between Plasma Lipoprotein Cholesterol Concentrations and the Pool Size and Metabolism of Cholesterol in Man

Ne, Miller; Pj, Nestel; Clifton‐Bligh, P.

doi:10.1007/978-1-4613-4220-5_68

Cited by 9 publications

(12 citation statements)

References 5 publications

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“…Thus, the HDL:LDL molar ratios to which peripheral cells are exposed in vivo are likely to be in a range similar to those at which a significant reduction in LDL uptake was observed in the present study. An inhibition of LDL uptake by HDL has been reported in cultured swine smooth muscle cells (20) and has also been noted in recent studies with vascular endothelium (6,47,48 (17). There is also increasing epidemiologic evidence for an important inverse relationship between plasma HDL concentration and coronary heart disease risk (49)(50)(51).…”

Section: Discussionmentioning

confidence: 66%

“…Despite this, the cholesterol content of extrahepatic tissues, measured directly in biopsies (13,14) or indirectly by isotope dilution analysis (15)(16)(17), has been only weakly correlated with the plasma total and LDL cholesterol concentrations. On the other hand, a recent study of hyperlipidemic subjects established that body cholesterol pool size shows a strong negative correlation with the plasma high density lipoprotein (HDL) concentration (17). Theoretically this could reflect a function of HDL in the removal of cholesterol from tissues, an inhibitory effect of HDL on cell cholesterol synthesis, an inhibition by HDL of the cellular uptake of LDL, or a combination of these mechanisms.…”

Section: Introductionmentioning

confidence: 99%

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Interaction between High Density and Low Density Lipoproteins during Uptake and Degradation by Cultured Human Fibroblasts

Miller¹,

Weinstein²,

Carew³

et al. 1977

J. Clin. Invest.

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107

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A B S T RA CT High density lipoprotein (HDL) inhibited the binding (trypsin-releasable radioactivity), internalization (cell-associated radioactivity after trypsinization), and degradation (TCA-soluble noniodide radioactivity) of 1251-low density lipoprotein (1251-LDL) by cultured normal human fibroblasts. At HDL:LDL molar ratios of 25:1 (protein ratios about 5:1), these parameters were reduced by about 25%. Unlabeled LDL was about 25 times more effective in reducing 125I-LDL binding, implying that if HDL and LDL bind at common sites the affinity of HDL for these sites is very low or that the interaction is on some other basis. The fractional reduction in 125I_ LDL binding at a given HDL: 1251-LDL ratio was independent of '25I-LDL concentration and occurred equally with fibroblasts from a subject with homozygous familial hypercholesterolemia. Reciprocally, the binding, internalization, and degradation of 125I_ HDL were reduced by LDL. Preincubation of fibroblasts with HDL (or LDL) reduced the subsequent binding of 1251-LDL (or 125I-HDL) during a second incubation. In other studies HDL reduced the net increase in cell cholesterol content induced by incubation with LDL. HDL alone had no net effect on cell cholesterol content.

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Section: Discussionmentioning

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Interaction between High Density and Low Density Lipoproteins during Uptake and Degradation by Cultured Human Fibroblasts

Miller¹,

Weinstein²,

Carew³

et al. 1977

J. Clin. Invest.

Self Cite

107

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“…This process, termed reverse cholesterol transport (4), was proposed to facilitate the removal of cholesterol from the body. Thus reverse cholesterol transport is one of several proposed mechanisms by which HDL provides protection from cardiovascular disease (5)(6)(7)(8)(9)(10).…”

mentioning

confidence: 99%

Overexpression of lecithin:cholesterol acyltransferase in transgenic rabbits prevents diet-induced atherosclerosis.

Hoeg

Santamarina-Fojo

Bérard

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

217

121

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Lecithin:cholesterol acyltransferase (LCAT) is a key plasma enzyme in cholesterol and high density lipoprotein (HDL) metabolism. Transgenic rabbits overexpressing human LCAT had 15-fold greater plasma LCAT activity than nontransgenic control rabbits. This degree of overexpression was associated with a 6.7-fold increase in the plasma HDL cholesterol concentration in LCAT transgenic rabbits. On a 0.3% cholesterol diet, the HDL cholesterol concentrations increased from 24 ± 1 to 39 + 3 mg/dl in nontransgenic control rabbits (n = 10; P < 0.05) and increased from 161 + 5 to 200 ± 21 mg/dl (P < 0.001) in the LCAT transgenic rabbits (n = 9). Although the baseline non-HDL concentrations of control (4 ± 3 mg/dl) and transgenic rabbits (18 ± 4 mg/dl) were similar, the cholesterol-rich diet raised the non-HDL cholesterol concentrations, reflecting the atherogenic very low density, intermediate density, and low density lipoprotein particles observed by gel filtration chromatography. The non-HDL cholesterol rose to 509 + 57 mg/dl in controls compared with only 196 ± 14 mg/dl in the LCAT transgenic rabbits (P < 0.005). The differences in the plasma lipoprotein response to a cholesterol-rich diet observed in the transgenic rabbits paralleled the susceptibility to developing aortic atherosclerosis. Compared with nontransgenic controls, LCAT transgenic rabbits were protected from diet-induced atherosclerosis with significant reductions determined by both quantitative planimetry (-86%; P < 0.003) and quantitative immunohistochemistry (-93%; P < 0.009). Our results establish the importance of LCAT in the metabolism of both HDL and apolipoprotein B-containing lipoprotein particles with cholesterol feeding and the response to diet-induced atherosclerosis. In addition, these findings identify LCAT as a new target for therapy to prevent atherosclerosis.

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“…HDL-cholesterol could derive from tissue cholesterol (3)(4)(5)(6) or from cholesterol of other lipoproteins originating in the liver or the intestine. Since the splanchnic territory both The plasma cholesterol removed by the splanchnic territory of the alcohol-fed animals could be excreted in the bile and lost in the feces, or it could recirculate in other lipoproteins or could accumulate in the liver.…”

Section: Discussionmentioning

confidence: 99%

“…The mechanism for this effect remains unknown. In vivo (3,4) and in vitro (5,6) studies indicate that high density lipoproteins (HDL) promote cholesterol efflux from the cells. Therefore, the observation that alcohol increases plasma concentrations of HDL (7,8), particularly the cholesterol moiety (HDL-C)' (9), suggested that it is via this lipoprotein fraction that ethanol enhances mobilization of tissue cholesterol for hepatic disposition into bile.…”

Section: Introductionmentioning

confidence: 99%

Effects of chronic ethanol intake on mobilization and excretion of cholesterol in baboons.

Karsenty¹,

Baraona²,

Savolainen³

et al. 1985

J. Clin. Invest.

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To investigate the effects of chronic ethanol administration on the mobilization and excretion of cholesterol, turnover and balance studies were carried out in baboons pair-fed cholesterolfree diets containing 50% of energy either as ethanol or as additional carbohydrate for several years. Ethanol feeding increased free cholesterol in all plasma lipoprotein fractions, and esterified cholesterol in very low density lipoprotein, intermediate density lipoprotein, and high density lipoprotein (HDL). The major increase occurred in HDL, mainly as esterified cholesterol. The latter was associated with decreased transfer of esterified cholesterol from HDL to low density lipoprotein. By contrast, the smaller increase in HDL-free cholesterol was associated with increased turnover in the plasma, increased splanchnic uptake, and increased fecal excretion of plasma cholesterol, mainly as neutral steroids. Cholesterol extraction predominated over release in the splanchnic vascular bed, suggesting that the excess of cholesterol excreted in the feces originated in extrasplanchnic tissues. Thus, these findings indicate that alcohol consumption favors mobilization of tissue free cholesterol for hepatic removal and excretion. By contrast the increase in HDL-cholesterol (mainly esterified) appears to be a poor indicator of cholesterol mobilization.

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Relationships Between Plasma Lipoprotein Cholesterol Concentrations and the Pool Size and Metabolism of Cholesterol in Man

Cited by 9 publications

References 5 publications

Interaction between High Density and Low Density Lipoproteins during Uptake and Degradation by Cultured Human Fibroblasts

Interaction between High Density and Low Density Lipoproteins during Uptake and Degradation by Cultured Human Fibroblasts

Overexpression of lecithin:cholesterol acyltransferase in transgenic rabbits prevents diet-induced atherosclerosis.

Effects of chronic ethanol intake on mobilization and excretion of cholesterol in baboons.

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