Cholestasis: Lamellar Structure of the Abnormal Human Serum Lipoprotein

Hamilton, Robert L.; Havel, Richard J.; Kane, John P.; Blaurock, A.E.; Sata, Teizo

doi:10.1126/science.172.3982.475

Cited by 191 publications

(62 citation statements)

References 22 publications

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“…2B) suggested that the VLDL/IDL fractions might contain lipoproteins consisting of apoB-free lamellar-free cholesterol/phospholipid particles, i.e. lipoprotein X-like particles of vesicular structure (24). Subsequently, SR-BI Tg mice were found to have functional LCAT deficiency (see below) in which lipoprotein X accumulates especially on a high fat diet (25,26).…”

Section: Sr-bi Expression In Sr-bi Tgmentioning

confidence: 99%

Liver-specific Overexpression of Scavenger Receptor BI Decreases Levels of Very Low Density Lipoprotein ApoB, Low Density Lipoprotein ApoB, and High Density Lipoprotein in Transgenic Mice

Wang

Arai

et al. 1998

Journal of Biological Chemistry

270

234

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Scavenger receptor BI (SR-BI) is known to mediate the selective uptake of high density lipoprotein (HDL) cholesteryl ester (CE) in liver and steroidogenic tissues. To evaluate the role of SR-BI in plasma lipoprotein metabolism, we have generated transgenic mice with liverspecific overexpression of murine SR-BI. On a chow diet SR-BI transgenic (SR-BI Tg) mice have decreased HDL-CE, apoA-I, and apoA-II levels; plasma triglycerides, low density lipoprotein (LDL) cholesterol, and very low density lipoprotein (VLDL) and LDL apoB were also decreased, compared with control mice. Turnover studies using non-degradable CE and protein labels showed markedly increased total and selective uptake of HDL-CE in the liver and increased HDL protein catabolism in both liver and kidney. To evaluate the changes in apoB further, mice were challenged with high fat, high cholesterol diets. In SR-BI Tg mice plasma apoB levels were only 3-15% of control levels, and the dietary increase in VLDL and LDL apoB was virtually abolished. These studies show that steady state overexpression of hepatic SR-BI reduces HDL levels and increases reverse cholesterol transport. They also indicate that SR-BI can play a role in the metabolism of apoB-containing lipoproteins. The dual effects of increased reverse cholesterol transport and lowering of apoB-containing lipoproteins that result from hepatic SR-BI overexpression could have anti-atherogenic consequences.The risk of coronary heart disease is inversely correlated with the levels of plasma high density lipoproteins (HDL) 1 (1, 2). HDL appears to transport cholesterol from peripheral tissues to the liver for catabolism and secretion (reverse cholesterol transport) (3, 4). A putative cell-surface receptor for this process has been identified (5). This receptor, scavenger receptor BI (SR-BI), mediates high affinity binding of HDL and the selective uptake of HDL cholesteryl ester (CE) (5), a process for delivery of cholesteryl ester into cells without degradation of HDL proteins (6). Furthermore, SR-BI mRNA and protein levels are highest in adrenal gland, ovary, testis, and liver, tissues that display greatest selective cholesteryl ester uptake from HDL (7-9). SR-BI expression in steroidogenic cells is regulated by hormones and mutations that alter cholesterol supply or metabolism in those tissues in vivo (8 -11). More recently, strong support for the role of SR-BI in HDL metabolism has been provided by studies of mice with a targeted mutation resulting in decreased SR-BI gene expression (12, 13). These mice demonstrate increased plasma HDL cholesterol, decreased adrenal cholesterol content (12, 13), and decreased hepatic fractional clearance rate (FCR) for HDL-CE (13), suggesting that SR-BI is the major molecule mediating HDL-CEselective uptake in the liver. By contrast, adenovirus-mediated, hepatic overexpression of SR-BI in mice results in depletion of plasma HDL and an increase in biliary cholesterol concentration (14). Although these studies nicely demonstrate the effect of acute overexpression of ...

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Section: Sr-bi Expression In Sr-bi Tgmentioning

confidence: 99%

Liver-specific Overexpression of Scavenger Receptor BI Decreases Levels of Very Low Density Lipoprotein ApoB, Low Density Lipoprotein ApoB, and High Density Lipoprotein in Transgenic Mice

Wang

Arai

et al. 1998

Journal of Biological Chemistry

270

234

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“…Agarose gel electrophoresis of lipoproteins in plasma and lipoprotein fractions was performed as described. 17 The distribution of particle diameters of negatively stained lipoproteins 20 was estimated from photographic prints at a magnification of 180,000 by a semiautomated method, utilizing a magnetic digitizer. Three points were marked on the circumference of each of 100 particles and the diameters were calculated by computer, programmed for a threepoint geometric algorithm.…”

Section: Analysesmentioning

confidence: 99%

Concentration and composition of lipoproteins in blood plasma of the WHHL rabbit. An animal model of human familial hypercholesterolemia.

et al. 1982

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“…28 Electron microscopy of lipoprotein fractions was performed on samples negatively stained with potassium phosphotungstate. 29 Particle diameters were measured on the photographic negative plates with a Nikon optical microcomparator (Model 6 C, Nippon Kogaku, KK, Tokyo, Japan). Apo B-48 antigen was identified by double immunodiffusion 30 against a rabbit antiserum specific for the apo B-48 lipoprotein.…”

Section: Lipoprotein Analysesmentioning

confidence: 99%

Remnants of lipoproteins of intestinal and hepatic origin in familial dysbetalipoproteinemia.

Kane¹,

Chen²,

Hamilton³

et al. 1983

Arteriosclerosis

102

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We used the low molecular weight form of apolipoprotein B (B-48) as a marker for the identification of remnant particles formed from chyiomicrons in the plasma of patients with familial dysbetalipoproteinemia. In the serum of patients fasted 14 hours, the d < 1.006 g/cm 3 lipoproteins of prebeta mobility, separated by starch block electrophoresis, contained only the primary hepatogenous species of apolipoprotein B (B-100), and their llpld composition resembled that of normal prebeta very low density lipoproteins. In contrast, the fraction with beta mobility contained both the B-48 and B-100 proteins; the B-48 protein was found primarily among the largest particles. All fractions of beta mobility were greatly enriched with choiesteryi esters. The beta fraction thus contains remnant particles which appear to originate both from chyiomicrons and hepatogenous very low density lipoproteins. It appears that these remnant particles share a common removal mechanism which is impaired in familial dysbetalipoproteinemia. (Arteriosclerosis 3:47-56, January/February 1983) amilial dysbetalipoproteinemia (F. dys.) (type III hyperlipoproteinemia) is now recognized as a disorder in which remnant-like particles, formed from triglyceride-rich lipoproteins, accumulate in plasma.12 Clinically, it is associated with arteriosclerosis of both the coronary and peripheral circulations. 3These remnant-like lipoprotein particles are enriched with choiesteryi esters 1 2 ' 4 and have beta mobility upon electrophoresis in agarose gel, in contrast with normal very low density lipoproteins (VLDL), which have prebeta mobility. The electrophoretic mobility of remnant particles is accounted for principally by deficiency of the C-apoproteins, which are normally the preponderant species in VLDL, with retention of appreciable quantities of less anionic apolipoprotein E (apo E). 5 The initial stages of intravascular lipolysis appear to proceed relatively normally. Removal of remnant particles from the plasma normally occurs rapidly by means of receptor-mediated endocytosis in the liver.2 In F. dys., however, there is

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Cholestasis: Lamellar Structure of the Abnormal Human Serum Lipoprotein

Cited by 191 publications

References 22 publications

Liver-specific Overexpression of Scavenger Receptor BI Decreases Levels of Very Low Density Lipoprotein ApoB, Low Density Lipoprotein ApoB, and High Density Lipoprotein in Transgenic Mice

Liver-specific Overexpression of Scavenger Receptor BI Decreases Levels of Very Low Density Lipoprotein ApoB, Low Density Lipoprotein ApoB, and High Density Lipoprotein in Transgenic Mice

Concentration and composition of lipoproteins in blood plasma of the WHHL rabbit. An animal model of human familial hypercholesterolemia.

Remnants of lipoproteins of intestinal and hepatic origin in familial dysbetalipoproteinemia.

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