The Metabolic Role of Lecithin: Cholesterol Acyltransferase: Perspectives from Pathology

Glomset, John A.; Norum, Kaare R.

doi:10.1016/b978-0-12-024911-4.50008-8

Cited by 439 publications

(152 citation statements)

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“…Lipoprotein lipase, by hydrolysis of TG-rich particles, generates surface remnant components (including phospholipid and cholesterol) which are taken up by HDL thus forming larger particles (37)(38)(39). Phospholipid and free cholesterol are substrates for lecithin: cholesterol acyltransferase, which generates cholesteryl ester that forms the core of larger, less dense HDL (40). It is thought that cholesteryl ester in the large HDL is exchanged for TG in very low-density lipoproteins through the action of the lipid transfer protein (4 1 -43).…”

Section: Discussionmentioning

confidence: 99%

High-Density Lipoprotein Subclass Distribution And Human Cord Blood Lipid Levels

1986

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ABSTRACT. The high-density lipoprotein (HDL) subclass distribution was examined by gradient gel electrophoresis (gge) in 154 human cord blood samples, and determinations of triglyceride, total cholesterol, and HDL-cholesterol levels were performed. Three distinct gge patterns were recognizable. The first pattern, termed the normal (gge) pattern, was distinguished by a prominent double peak in the (HDL2,),, region and a pronounced peak in the (HDL3b)gge region. Minor peaks, or shoulders, were also seen in the (HDLZb)gge and (HDL3Jae regions, and a valley was present in the (HDL3,),,, region. This pattern was associated with normal lipid levels for cord blood plasma (mean triglycerides: 30-42 mg/dl; mean total cholesterol 62-85 mg/dl; mean HDL-cholesterol: 34-41 mg/ dl).The second pattern, termed the 2b(gge) pattern, contained a major peak in the ( H D L z~)~~, region rather than the shoulder seen in the normal (gge) pattern, while the (HDL2.)gge, (HDL3b),e, and (HDL3,),, regions were less pronounced. This pattern was associated with elevated total cholesterol and HDL-C levels (means 85-102 and 49-56 mg/dl, respectively). The third pattern, termed the 3b(gge) pattern, was characterized by a paucity of material in the (HDL2,,),, region, a single peak in the (HDLza),, region, and either a relative increase in the (HDL3b),e region, or a simultaneous increase in both (HDLs~),~ and (HDL3e),e. This pattern was associated with elevated triglyceride levels (means 78-88 mg/dl) and decreased HDL-C levels (means 20-30 mg/dl). Only two infants had a simultaneous elevation of triglycerides and total cholesterol and both cases exhibited the 3b(gge) pattern. Our study demonstrates that although the triglyceride and cholesterol levels in the newborn are much lower than those in adults, they are the important factors associated with the HDL subclass distribution. Elevated cholesterol was related to increased particles in the (HDL2b), region while elevated triglyceride levels were associated with a decrease in (HDL2b+2a)gge particles and a concomitant increase in (HDLsb),, particles. (Pediatr Res 20: 487-491, 1986) Abbreviations HDL, high-density lipoproteins TG, triglyceride TC, total cholesterol HDL-C, HDL-cholesterol gge, gradient gel electrophoresis CB, cord blood Received October 7, 1985: accepted January 23, 1986. Address correspondence and requests for reprints to Orsolya Genzel-Boroviczeny, M.D., Donner Laboratory, 1-213, University of California, Berkeley, CA 94720.This work was supported by NIH Program Project Grant HL 18574 from the National Heart, Lung, and Blood Institute of the National Institutes of Health and NIH National Research Service Award Training Grant HL 07279.There is growing evidence that HDL, and in particular the HDL2 subclass, have a protective role in the process of atherogenesis (1-3). In contrast to adults, in whom low density lipoproteins predominate, HDL is the predominant lipoprotein species in human CB (4-10). Davis et al. (4) found that in healthy term infants with lipoprotein levels below 10...

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Section: Discussionmentioning

confidence: 99%

High-Density Lipoprotein Subclass Distribution And Human Cord Blood Lipid Levels

1986

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“…This is a process in which excess cholesterol from peripheral tissue and macrophages/foam cells is taken up and processed in HDL particles and later delivered to the liver, before being excreted in the bile as free cholesterol or after transformation into bile acids. 1 This process, the principal way by which the body eliminates cholesterol, relies on specific interactions between HDL particles and peripheral cells (cholesterol efflux) on the one hand and hepatocytes (HDL cholesterol uptake) on the other Abbreviations: abca1, ATP-binding cassette, subfamily A, member 1; abcb4, ATP-binding cassette b4; abcb11/bsep, ATP-binding cassette b11/bile salt export pump; abcg1, ATP-binding cassette g1; abcg5/abcg8, ATP-binding cassette g5/g8; apoA-I, apolipoprotein A-I; ATP, adenosine triphosphate; HDL, high-density lipoprotein; hmgcr, 3-hydroxy-3-methylglutaryl-coenzyme A reductase; mRNA, messenger RNA; ntcp, Na þ -taurocholate cotransporting polypeptide; oatp, organic anion transport polypeptide; P2Y 13 , purinergic receptor P2Y, G-protein-coupled 13; RCT, reverse cholesterol transport; SR-BI, scavenger receptor class B, type I.…”

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confidence: 99%

P2Y13 Receptor Is Critical for Reverse Cholesterol Transport

et al. 2010

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A major atheroprotective functionality of high-density lipoproteins (HDLs) is to promote ''reverse cholesterol transport'' (RCT). In this process, HDLs mediate the efflux and transport of cholesterol from peripheral cells and its subsequent transport to the liver for further metabolism and biliary excretion. We have previously demonstrated in cultured hepatocytes that P2Y 13 (purinergic receptor P2Y, G protein-coupled, 13) activation is essential for HDL uptake but the potential of P2Y 13 as a target to promote RCT has not been documented. Here, we show that P2Y 13 -deficient mice exhibited a decrease in hepatic HDL cholesterol uptake, hepatic cholesterol content, and biliary cholesterol output, although their plasma HDL and other lipid levels were normal. These changes translated into a substantial decrease in the rate of macrophage-to-feces RCT. Therefore, hallmark features of RCT are impaired in P2Y 13 -deficient mice. Furthermore, cangrelor, a partial agonist of P2Y 13 , stimulated hepatic HDL uptake and biliary lipid secretions in normal mice and in mice with a targeted deletion of scavenger receptor class B type I (SR-BI) in liver (hypomSR-BIknockout liver ) but had no effect in P2Y 13 knockout mice, which indicate that P2Y 13 -mediated HDL uptake pathway is independent of SR-BI-mediated HDL selective cholesteryl ester uptake. Conclusion: These results establish P2Y 13 as an attractive novel target for modulating RCT and support the emerging view that steady-state plasma HDL levels do not necessarily reflect the capacity of HDL to promote RCT.

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“…Comme l'Agneau préruminant (Leat, Kubassek et Butress, 1976) (Stead et Welch, 1975 ;Forte, Bell-Quint et Cheng, 1981) et de l'Homme (Fruchart et Sezille, 1977) (1972). D'après ces auteurs, la LCAT bovine se distinguerait de la LCAT humaine (Glomset et Norum, 1973) (Skipski, 1972) …”

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