Lipid Transfer Inhibitor Protein Activity Deficiency in Normolipidemic Uremic Patients on Continuous Ambulatory Peritoneal Dialysis

Serdyuk, A. P.; Morton, Richard E.

doi:10.1161/01.atv.17.9.1716

Cited by 17 publications

(20 citation statements)

References 38 publications

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“…CETP plus near-physiological levels of LTIP replicated the preferential transfer of CE from HDL typically seen in plasma, whereas CETP alone could not. These findings are consistent with our recent observations in an LTIP activitydeficient patient population, 39 where CETP-mediated CE fluxes from LDL and HDL to VLDL were equivalent when the lipoproteins are compared on the basis of their CE content. We suggest that the apparent preferential transfer of HDL lipids by CETP in plasma 38,39,53,54 reflects the activity of LTIP, not the lipoprotein selectivity of CETP.…”

Section: Discussionsupporting

confidence: 93%

“…This lack of lipoprotein specificity by CETP is not an in vitro artifact due to lipoprotein isolation since no preference for HDL is seen in whole plasma from patients deficient in LTIP activity. 39 We have recently observed that increased negative charge on lipoproteins results in increased stable CETP-lipoprotein binding, but that the effects of these modification on CETP activity are highly dependent on the nature of the derivatization itself (Morton R.E. and Greene D.J., unpublished observations).…”

Section: Discussionmentioning

confidence: 99%

“…23 A preference value of Ϸ2 is similar to that observed in intact, control plasma. 39 The lack of preferential CE net transfer from HDL seen in Figure 1 was not unique to the ratio of lipoproteins present in normal plasma. When the LDL to HDL ratio in the assay was varied Ͼ4-fold while holding the sum of these lipoproteins constant, there was minimal preferential transfer of CE from HDL in the absence of LTIP ( Figure 2A).…”

Section: Participation Of Ldl and Hdl In Ce Mass Transfermentioning

confidence: 90%

“…37 Furthermore, in whole plasma, HDL is the major donor of CE to VLDL compared with LDL when transfers are expressed relative to the CE content of these lipoproteins. 38,39 In contrast to these observations, some studies suggest that HDL is not a preferential substrate for CETP. Under equilibrium conditions, steady-state binding studies indicate that VLDL, LDL, and HDL have very similar affinities for CETP, and the number of CETP "binding sites" is nearly the same for these lipoproteins when expressed relative to their phospholipid surface area.…”

mentioning

confidence: 96%

“…25 We have shown that there is no preferential transfer of CE from HDL in plasma from patients undergoing continuous peritoneal dialysis, in contrast to control plasma. 39 A possible explanation for these findings is that CETP has no inherent preference for HDL as a substrate, but rather, the preferential transfer of CE from HDL seen in control subjects is due to the action of LTIP, whose activity is greatly diminished in these patients.…”

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confidence: 99%

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Lipid Transfer Inhibitor Protein Defines the Participation of Lipoproteins in Lipid Transfer Reactions

Serdyuk

Morton

1999

ATVB

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Abstract-Cholesteryl ester transfer protein (CETP) catalyzes the net transfer of cholesteryl ester (CE) between lipoproteins in exchange for triglyceride (heteroexchange). It is generally held that CETP primarily associates with HDL and preferentially transfers lipids from this lipoprotein fraction. This is illustrated in normal plasma where HDL is the primary donor of the CE transferred to VLDL by CETP. However, in plasma deficient in lipid transfer inhibitor protein (LTIP) activity, HDL and LDL are equivalent donors of CE to VLDL (Arterioscler Thromb Vasc Biol. 1997;17:1716 -1724. Thus, we have hypothesized that the preferential transfer of CE from HDL in normal plasma is a consequence of LTIP activity and not caused by a preferential CETP-HDL interaction. We have tested this hypothesis in lipid mass transfer assays with partially purified CETP and LTIP, and isolated lipoproteins. With a physiological mixture of lipoproteins, the preference ratio (PR, ratio of CE mass transferred from a lipoprotein to VLDL versus its CE content) for HDL and LDL in the presence of CETP alone was Ϸ1 (ie, no preference). Fourfold variations in the LDL/HDL ratio or in the levels of HDL in the assay did not result in significant preferential transfer from any lipoprotein. On addition of LTIP, the PR for HDL was increased up to 2-fold and that for LDL decreased in a concentration-dependent manner.Under all conditions where LDL and HDL levels were varied, LTIP consistently resulted in a PR Ͼ1 for CE transfer from HDL. Short-term experiments with radiolabeled lipoproteins and either partially purified or homogenous CETP confirmed these observations and further demonstrated that CETP has a strong predilection to mediate homoexchange (bidirectional transfer of the same lipid) rather than heteroexchange (CE for TG); LTIP had no effect on the selection of CE or TG by CETP or its mechanism of action. The ability of CETP to facilitate the remodeling of lipoprotein composition endows an important role to this protein in the intravascular metabolism of lipoproteins. CETP participates in determining the ratio of HDL 2 to HDL 3 , 3-5 facilitates the loss of apo A-I from ␣-migrating HDL resulting in an increase of pre␤ HDL, 6 and enhances reverse cholesterol transport. 2,7,8 CETP also affects the level of LDL subfractions and their interaction with the LDL receptor, 9 -13 and facilitates the conversion of VLDL to LDL. 1,14 Many of these observations have been verified and extended through studies of humans who are genetically deficient in CETP 15,16 and in transgenic mice bearing the CETP transgene. 17,18 Overall, CETP activity significantly influences the structure and function of the lipoproteins with which it interacts.We and others have suggested that the function of CETP, that is, its capacity to affect changes in the composition of individual lipoprotein fractions, is modulated by a second plasma protein, lipid transfer inhibitor protein (LTIP). 19 -24 LTIP is a LDL-associated protein of ϳ30 kd that preferentially reduces the action of C...

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Participation Of Ldl and Hdl In Ce Mass Transfermentioning

confidence: 90%

mentioning

confidence: 96%

mentioning

confidence: 99%

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Lipid Transfer Inhibitor Protein Defines the Participation of Lipoproteins in Lipid Transfer Reactions

Serdyuk

Morton

1999

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Reverse cholesterol transport in diabetes mellitus

Quintão

Medina

Passarelli

2000

Diabetes Metab. Res. Rev.

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There are epidemiological data and experimental animal models relating the development of premature atherosclerosis with defects of the reverse cholesterol transport (RCT) system. In this regard, the plasma concentrations of the high density lipoprotein (HDL) subfractions, of cholesteryl ester transfer protein (CETP), as well as the activity of the enzyme lecithin-cholesterol acyl transferase (LCAT) play critical roles. However, there has been plenty of evidence that atherosclerosis in diabetes mellitus (DM) is ascribed to a greater arterial wall cell uptake of modified apoB-containing lipoproteins whereas a primary or predominant defect of the RCT system is still a subject of debate. In other words, in spite of the fact that in DM the composition and rates of metabolism of the HDL particles are greatly altered and display a diminished in vitro efficiency to remove cell cholesterol, definitive in vivo demonstration of the importance of this fact in atherogenesis is lacking. Furthermore, the roles played by LCAT and CETP in RCT in DM are difficult to interpret because the in vitro procedures of measurement utilized have either been inadequate, or inappropriately interpreted. Knock-out or transgenic mice are much needed models to investigate the roles of LCAT, CETP, phospholipid transfer protein (PLTP), and of a CETP inhibitor in the development of atherosclerosis of experimental DM.

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Transcriptional regulation of the apolipoprotein F (ApoF) gene by ETS and C/EBPα in hepatoma cells

et al. 2015

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Lipid Transfer Inhibitor Protein Activity Deficiency in Normolipidemic Uremic Patients on Continuous Ambulatory Peritoneal Dialysis

Cited by 17 publications

References 38 publications

Lipid Transfer Inhibitor Protein Defines the Participation of Lipoproteins in Lipid Transfer Reactions

Lipid Transfer Inhibitor Protein Defines the Participation of Lipoproteins in Lipid Transfer Reactions

Reverse cholesterol transport in diabetes mellitus

Transcriptional regulation of the apolipoprotein F (ApoF) gene by ETS and C/EBPα in hepatoma cells

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