Journal articles: 'LDL transfer'

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Surya, Ingrid I., Gertie Gorter, and Jan Willem N. Akkerman. "Arachidonate Transfer Between Platelets and Lipoproteins." Thrombosis and Haemostasis 68, no. 06 (1992): 719–26. http://dx.doi.org/10.1055/s-0038-1646350.

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SummaryAlthough platelets have specific bindingsites for LDL and HDL, it is doubtful whether lipoproteins modulate platelet functions via receptor-mediated processes. We investigated platelet-lipoprotein interaction during prolonged incubation with concentrations of LDL and HDL that saturate the bindingsites within a few minutes. When [3H]arachidonate-labeled human platelets were incubated for 4 h with lipoproteins, part of the 3H-radioactivity transferred to LDL and to a lesser extent to HDL. The transfer was temperature-sensitive, unaffected by modification of lysine in LDL or indomethacin treatment of the platelets, and almost irreversible. [3H]arachidonate transfer to lipoproteins could be mimicked by incubating platelets with a high concentration of fatty acid free albumin. This showed, that the loss of 3H-radioactivity reflected a decrease in endogenous arachidonate, leading to impaired aggregation, secretion and thromboxane B2 formation in platelets after stimulation with thrombin but not with arachidonate. Thus, the decrease in platelet functions seen after long incubation with HDL is caused by depletion of platelet arachidonate. Despite an even stronger arachidonate depletion by LDL, this lipoprotein initiated arachidonate metabolism and secretion independent of specific binding sites for LDL on the platelet. Surprisingly, the major part of the secretion was preserved when the formation of prostaglandin endoperoxides/ thromboxane A2 was inhibited with indomethacin. These findings argue against a role for LDL and HDL receptors in the modulation of platelet functions and are more in favor of lipid exchange processes between platelets and lipoproteins.

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YANG, Min, David S. LEAKE, and Catherine A. RICE-EVANS. "Non-oxidative modification of native low-density lipoprotein by oxidized low-density lipoprotein." Biochemical Journal 316, no. 2 (June 1, 1996): 377–80. http://dx.doi.org/10.1042/bj3160377.

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The oxidative modification of low-density lipoprotein (LDL) has been implicated in the pathogenesis of atherosclerosis, although little is known as yet about the precise mechanism of oxidation in vivo. The studies presented here demonstrate that, in the absence of cells or transition metals, oxidized LDL can modify native LDL through co-incubation in vitro such as to increase its net negative charge, in a concentration-dependent manner. The interaction is not inhibited by peroxyl radical scavengers or metal chelators, precluding the possibility that the modification of native LDL by oxidized LDL is through an oxidative process. Studies with radioiodinated oxidized LDL showed no transfer of radioactivity to the native LDL, demonstrating that fragmentation of protein and the transfer of some of the fragments does not account for the modified charge on the native LDL particle. The adjacency of native to oxidized LDL in the arterial wall may be a potential mechanism by which the altered recognition properties of the apolipoprotein B-100 may arise rapidly without oxidation or extensive modification of the native LDL lipid itself.

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Lundberg, B. B., and L. A. Suominen. "Physicochemical transfer of [3H]cholesterol from plasma lipoproteins to cultured human fibroblasts." Biochemical Journal 228, no. 1 (May 15, 1985): 219–25. http://dx.doi.org/10.1042/bj2280219.

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The transfer of free cholesterol from [3H]cholesterol-labelled plasma lipoproteins to cultured human lung fibroblasts was studied in a serum-free medium. The uptake of [3H]cholesterol depended upon time of incubation, concentration of lipoprotein in the medium, and temperature. Modified (reduced and methylated) low-density lipoprotein (LDL), which did not enter the cells by the receptor pathway, gave a somewhat lower transfer rate than unmodified LDL, but if the transfer values for native LDL were corrected for the receptor-mediated uptake of cholesterol the difference was eliminated. The initial rates of transfer of [3H]cholesterol from LDL and high-density lipoprotein (HDL) were of the same order of magnitude (0.67 +/- 0.05 and 0.75 +/- 0.06 nmol of cholesterol/h per mg of cell protein, respectively) while that from very-low-density lipoprotein (VLDL) was much lower (0.23 +/- 0.02 nmol of cholesterol/h per mg) (means +/- S.D., n = 5). The activation energy for transfer of cholesterol from reduced, methylated LDL to fibroblasts was determined to be 57.5 kJ/mol. If albumin was added to the incubation medium the transfer of [3H]cholesterol was enhanced, while that of [14C]dipalmitoyl phosphatidylcholine was decreased compared with the protein-free system. The results demonstrate that, in spite of its low water solubility, free cholesterol can move from lipoproteins to cellular membranes, probably by aqueous diffusion. We propose that physicochemical transfer of free cholesterol may be a significant mechanism for net uptake of the sterol into the artery during atherogenesis.

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Hall, Justin, and Xiayang Qiu. "Structural and biophysical insight into cholesteryl ester-transfer protein." Biochemical Society Transactions 39, no. 4 (July 20, 2011): 1000–1005. http://dx.doi.org/10.1042/bst0391000.

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CETP (cholesteryl ester-transfer protein) is essential for neutral lipid transfer between HDL (high-density lipoprotein) and LDL (low-density lipoprotein) and plays a critical role in the reverse cholesterol transfer pathway. In clinical trials, CETP inhibitors increase HDL levels and reduce LDL levels, and therefore may be used as a potential treatment for atherosclerosis. In this review, we cover the analysis of CETP structure and provide insights into CETP-mediated lipid transfer based on a collection of structural and biophysical data.

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Kostner, G. M., F. Krempler, H. Dieplinger, R. Zechner, I. Teubl, and F. Sandhofer. "Altered metabolism of low density lipoprotein in humans after prolonged incubation in plasma." Clinical Science 68, no. 4 (April 1, 1985): 411–18. http://dx.doi.org/10.1042/cs0680411.

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1. Lecithin: cholesterol acyltransferase (LCAT) in combination with exchange and transfer proteins is known to alter the composition of all plasma lipoprotein fractions. 2. Human plasma from healthy donors was incubated for 24 h at 37°C in the absence and at 4°C and at 37°C in the presence of the LCAT inhibitors sodium iodoacetate (5 mmol/l), and the low density lipoprotein fractions (LDL) were isolated. 3. LDL isolated from LCAT-active plasma (LDL-a) exhibited pronounced alterations in their surface material: the relative content of phospholipids and of free cholesterol was reduced and the content of tetramethylurea-soluble apolipoproteins was increased. LDL isolated from plasma incubated at 37°C with or without sodium iodoacetate showed significantly increased triglyceride concentrations. 4. The LDL fractions from LCAT-active and LCAT-inactive (LDL-i) incubates were iodinated with 125I and 131I respectively, and their metabolic behaviour was studied in humans. 5. LDL-a was cleared from circulation at a slower rate as compared with LDL-i (t1/2 = 3.17 ± 0.47 vs 2.88 ± 0.45 days). The apparent fractional catabolic rate of LDL-a, calculated according to a two-pool model, was reduced by 22.2 ± 3.1%. Comparing LDL-a with LDL isolated from LCAT-inactive plasma which had been incubated at 37°C, the changes in the metabolic variables were less pronounced. 6. It is concluded that physiological alterations of the chemical compositions, caused by LCAT and exchange/transfer proteins, influence the metabolism of LDL.

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Murdoch, Susan J., Molly C. Carr, Hal Kennedy, John D. Brunzell, and John J. Albers. "Selective and independent associations of phospholipid transfer protein and hepatic lipase with the LDL subfraction distribution." Journal of Lipid Research 43, no. 8 (August 2002): 1256–63. http://dx.doi.org/10.1194/jlr.m100373-jlr200.

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Phospholipid transfer protein (PLTP), hepatic lipase (HL), and lipoprotein lipase (LPL) have all been reported to be intricately involved in HDL metabolism but the effect of PLTP on the apolipoprotein B-containing lipoproteins relative to that of HL and LPL has not been established. Due to our previous observation of a positive correlation of PLTP activity with plasma apoB and LDL cholesterol, the relationship of PLTP with the LDL subfractions was investigated and compared with that of HL and LPL. Plasma lipoproteins from 50 premenopausal women were fractionated by density gradient ultracentrifugation. Correlations were calculated between the cholesterol concentration of each fraction and plasma PLTP, HL, and LPL activity. Plasma PLTP activity was highly, positively, and selectively correlated with the cholesterol concentration of the buoyant LDL/dense IDL fractions, yet demonstrated a complete absence of an association with the dense LDL fractions. In contrast, HL was positively correlated with the dense LDL fractions but showed no association with buoyant LDL. LPL was also positively correlated with several buoyant LDL fractions; however, the correlations were weaker than those of PLTP. PLTP and LPL were positively correlated and HL was negatively correlated with HDL fractions.The results suggest that PLTP and HL may be important and independent determinants of the LDL subpopulation density distributions.

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Dobner, Petra, and Bernd Engelmann. "Low-density lipoproteins supply phospholipid-bound arachidonic acid for platelet eicosanoid production." American Journal of Physiology-Endocrinology and Metabolism 275, no. 5 (November 1, 1998): E777—E784. http://dx.doi.org/10.1152/ajpendo.1998.275.5.e777.

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After the rapid extracorporal reduction of plasma low-density lipoprotein (LDL) by LDL apheresis, the percentages of arachidonic acid (AA)-containing species of phosphatidylcholine (PC) were lowered in the plasma of patients with hypercholesterolemia. The same PC species with AA were also decreased in the patient’s platelets. Thus the supply of phospholipid-bound AA from LDL to the platelets was probably diminished after the apheresis. We therefore analyzed the concentration dependence of the transfer of phospholipid-bound AA from LDL to the platelets under in vitro conditions. The amount of [14C]AA-PC transferred to platelets strongly increased upon elevation of LDL from 0.1 to 1 mg protein/ml, with a less marked elevation being noted at higher LDL concentrations. After stimulation with thrombin (0.5 U/ml), 7.1% ([14C]AA-PC) and 10.6% ([14C]AA-phosphatidylethanolamine) of the14C transferred from LDL to the platelets were recovered in the eicosanoids [14C]thromboxane B2(TxB2) plus 12-[14C]hydroxyeicosatetraenoic acid. Experimental increases and reductions of the [14C]AA-PC import were associated with comparable modifications in the [14C]TxB2production of the platelets. Accordingly, the import of phospholipid-bound [14C]AA is a necessary prerequisite for the formation of14C-labeled eicosanoids. In summary, the transfer of phospholipids from LDL to the platelets markedly varies within the physiological range of lipoprotein concentrations. LDL contributes to platelet eicosanoid formation by supplying platelets with phospholipid-bound AA.

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Ota, Y., K. Kugiyama, S. Sugiyama, T. Matsumura, T. Terano, and H. Yasue. "Complexes of apoA-1 with phosphatidylcholine suppress dysregulation of arterial tone by oxidized LDL." American Journal of Physiology-Heart and Circulatory Physiology 273, no. 3 (September 1, 1997): H1215—H1222. http://dx.doi.org/10.1152/ajpheart.1997.273.3.h1215.

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The aim of this study was to determine whether apolipoprotein A-1 (apoA-1) may suppress the vasomotor dysregulation by oxidized low-density lipoprotein (ox-LDL), which is known to be an atherogenic lipoprotein. The isolated porcine coronary arterial rings and the cultured endothelial cells from the porcine coronary arteries were exposed to ox-LDL in the presence or absence of complexes of apoA-1 with dimyristoylphosphatidylcholine (DMPC/apoA-1), apoA-1 alone, or DMPC alone. DMPC/apoA-1 but not apoA-1 alone or DMPC alone was found to suppress both impairment of endothelium-dependent arterial relaxation and vasocontraction caused by ox-LDL in the isolated porcine coronary arterial rings suspended in organ chambers. DMPC/apoA-1 absorbed lysophosphatidylcholine (LPC) from ox-LDL and decreased the transfer of LPC from ox-LDL to the surface membrane of the cultured endothelial cells, but apoA-1 alone and DMPC alone had no effect. High-density lipoprotein exerted the protective actions mimicking those observed in DMPC/apoA-1. Thus DMPC/apoA-1 decreased the transfer of LPC from ox-LDL to surface membrane by absorbing LPC, leading to the suppression of ox-LDL-induced dysregulation of endothelium-dependent arterial tone. Therefore, apoA-1 appears to require formation of the complexes with phospholipids to prevent the endothelial dysfunction caused by ox-LDL.

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Fan, Zhenmin, Xiao Liu, Peng Zhang, Jiang Gu, Xia Ye, and Xiaoyan Deng. "Transfer of Low-Density Lipoproteins in Coronary Artery Bifurcation Lesions with Stenosed Side Branch: Numerical Study." Computational and Mathematical Methods in Medicine 2019 (October 15, 2019): 1–10. http://dx.doi.org/10.1155/2019/5297284.

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Evidence from clinical data suggests that the stenotic side branch (SB) is one of the key predictors for SB occlusion-based adverse events. In this study, we hypothesized that coronary bifurcations with stenotic SB might lead to severe concentration polarization of atherogenic lipids, such as the low-density lipoproteins (LDL), motivating the adverse events in the clinic. To confirm this hypothesis, this work numerically investigated the transport of LDL in different bifurcation lesions based on the Medina classification with various location and stenosis severities. The results showed that the coronary bifurcations with stenotic SB might be suffering more serious concentration polarization of LDL on the luminal surface of the SB due to higher level of LDL concentrations. Moreover, compared to the other bifurcation lesion types, the type (1,0,1) had the highest luminal surface LDL concentration along the SB and the highest degree of risk to enhance the process of atherosclerosis. In addition, this study also showed that the luminal surface LDL concentration increased with elevated stenosis severity. The type (1,0,1) with the severe stenosis (75% diameter reduction) had the highest concentration at the SB. In conclusion, these results suggested that both location of lesions and stenosis severities had great influence on the distribution of LDL on the luminal surface of the SB. Therefore, the estimation of disease severity and the interventional therapy should be carried out not only according to the stenosis severities in clinic. Moreover, compared to the other bifurcation lesion types, the type (1,0,1), rather than the type (1,1,1) as usually considered, had the highest luminal surface LDL concentration along the SB and the highest degree of risk to enhance the process of atherosclerosis.

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ENGELMANN, Bernd, Christine KÖGL, Robert KULSCHAR, and Barbara SCHAIPP. "Transfer of phosphatidylcholine, phosphatidylethanolamine and sphingomyelin from low- and high-density lipoprotein to human platelets." Biochemical Journal 315, no. 3 (May 1, 1996): 781–89. http://dx.doi.org/10.1042/bj3150781.

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Following a 1 h incubation of human platelets with low-density lipoprotein (LDL) labelled in the apoprotein fraction (125I-apoB) or in phospholipid fractions [14C-labelled phosphatidylcholine (PC), phosphatidylethanolamine (PE) or sphingomyelin (SM)], the percentage of total 14C associated with the cells was about 3-fold higher than the percentage of 125I. Differences in temperature sensitivity also indicated differential interactions of phospholipids and apoprotein with platelets. In order to assess the amount of [14C]phospholipid transferred from LDL or high-density lipoprotein (HDL) to the cells, the quantity of bound lipoproteins was estimated by adding an excess of unlabelled lipoprotein, or by selectively degrading LDL- and HDL-associated [14C]PC and [14C]PE with phospholipase C. Incubation of platelets with LDL or HDL containing pyrenedecanoic acid-labelled PC or SM (py-PC, py-SM) increased pyrene monomer fluorescence, indicating incorporation of the phospholipids into platelets. With HDL as donor, incorporation of py-SM was greater than uptake of py-PC. Pretreating platelets with elastase dose-dependently inhibited uptake of py-SM and py-PC. Treatment of cells with phospholipase C indicated that the uptake of [14C]PC by platelets, and not the binding of lipoproteins to the cells, was partially inhibited by elastase. In conclusion, LDL and HDL rapidly deliver SM, PC and PE to platelets. Incorporation of LDL-derived phospholipids into platelets is unlikely to be mediated by endocytosis of lipoprotein particles. The uptake of the two choline-containing phospholipids appears to require the presence of specialized platelet membrane protein(s).

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Groener, J. E., R. W. Pelton, and G. M. Kostner. "Improved estimation of cholesteryl ester transfer/exchange activity in serum or plasma." Clinical Chemistry 32, no. 2 (February 1, 1986): 283–86. http://dx.doi.org/10.1093/clinchem/32.2.283.

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Abstract This simple, routine assay for measuring cholesteryl ester transfer/exchange activity in human plasma is based on the removal of interfering lipoproteins--very-low-density (VLDL) and low-density lipoproteins (LDL)--by precipitation with polyethylene glycol. High-density lipoproteins (HDL) in the samples do not affect the results. The supernate after precipitation is mixed with [14C]cholesteryl ester-labeled LDL as donor and with HDL as the acceptor for the cholesteryl ester. After incubation for 16 h at 37 degrees C, LDL is separated from HDL by precipitation with dextran sulfate and the radioactivity measured in the supernate, which contains the HDL. The assay is applicable to samples containing as much as 10 mmol of triglycerides per liter. The within-assay CV was 2.7%, the day-to-day CV 6.8%. Results compared well with those by conventional procedures.

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Lundahl, Björn, Camilla Skoglund-Andersson, Muriel Caslake, Dorothy Bedford, Philip Stewart, Anders Hamsten, Christopher J. Packard, and Fredrik Karpe. "Microsomal triglyceride transfer protein −493T variant reduces IDL plus LDL apoB production and the plasma concentration of large LDL particles." American Journal of Physiology-Endocrinology and Metabolism 290, no. 4 (April 2006): E739—E745. http://dx.doi.org/10.1152/ajpendo.00376.2005.

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The microsomal triglyceride transfer protein (MTP) is essential for the synthesis and secretion of apolipoprotein B (apoB)-containing lipoproteins. We investigated the role the MTP −493G/T gene polymorphism in determining the apoB-100 secretion pattern and LDL heterogeneity in healthy human subjects. Groups of carriers of the T and the G variants ( n = 6 each) were recruited from a cohort of healthy 50-yr-old men. Kinetic studies were performed by endogenous [2H3]leucine labeling of apoB and subsequent quantification of the stable isotope incorporation. apoB production rates, metabolic conversions, and eliminations were calculated by multicompartmental modeling (SAAM-II). LDL subfraction distribution was analyzed in the entire cohort ( n = 377). Carriers of the MTP −493T allele had lower plasma LDL apoB and lower concentration of large LDL particles [LDL-I: 136 ± 57 (TT) vs. 175 ± 55 (GG) mg/l, P < 0.01]. Kinetic modeling suggested that MTP −493T homozygotes had a 60% lower direct production rate of intermediate-density lipoprotein (IDL) plus LDL compared with homozygotes for the G allele ( P < 0.05). No differences were seen in production rates of large and small VLDL, nor were there any differences in metabolic conversion or elimination rates of apoB between the genotype groups. This study shows that a polymorphism in the MTP gene affects the spectrum of endogenous apoB-containing lipoprotein particles produced in humans. Reduced direct production of LDL plus IDL appears to be related to lower plasma concentrations of large LDL particles.

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Cedó, Lídia, Jari Metso, David Santos, Annabel García-León, Núria Plana, Sonia Sabate-Soler, Noemí Rotllan, et al. "LDL Receptor Regulates the Reverse Transport of Macrophage-Derived Unesterified Cholesterol via Concerted Action of the HDL-LDL Axis." Circulation Research 127, no. 6 (August 28, 2020): 778–92. http://dx.doi.org/10.1161/circresaha.119.316424.

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Rationale: The HDL (high-density lipoprotein)-mediated stimulation of cellular cholesterol efflux initiates macrophage-specific reverse cholesterol transport (m-RCT), which ends in the fecal excretion of macrophage-derived unesterified cholesterol (UC). Early studies established that LDL (low-density lipoprotein) particles could act as efficient intermediate acceptors of cellular-derived UC, thereby preventing the saturation of HDL particles and facilitating their cholesterol efflux capacity. However, the capacity of LDL to act as a plasma cholesterol reservoir and its potential impact in supporting the m-RCT pathway in vivo both remain unknown. Objective: We investigated LDL contributions to the m-RCT pathway in hypercholesterolemic mice. Methods and Results: Macrophage cholesterol efflux induced in vitro by LDL added to the culture media either alone or together with HDL or ex vivo by plasma derived from subjects with familial hypercholesterolemia was assessed. In vivo, m-RCT was evaluated in mouse models of hypercholesterolemia that were naturally deficient in CETP (cholesteryl ester transfer protein) and fed a Western-type diet. LDL induced the efflux of radiolabeled UC from cultured macrophages, and, in the simultaneous presence of HDL, a rapid transfer of the radiolabeled UC from HDL to LDL occurred. However, LDL did not exert a synergistic effect on HDL cholesterol efflux capacity in the familial hypercholesterolemia plasma. The m-RCT rates of the LDLr (LDL receptor)-KO (knockout), LDLr-KO/APOB100, and PCSK9 (proprotein convertase subtilisin/kexin type 9)-overexpressing mice were all significantly reduced relative to the wild-type mice. In contrast, m-RCT remained unchanged in HAPOB100 Tg (human APOB100 transgenic) mice with fully functional LDLr, despite increased levels of plasma APO (apolipoprotein)-B–containing lipoproteins. Conclusions: Hepatic LDLr plays a critical role in the flow of macrophage-derived UC to feces, while the plasma increase of APOB-containing lipoproteins is unable to stimulate m-RCT. The results indicate that, besides the major HDL-dependent m-RCT pathway via SR-BI (scavenger receptor class B type 1) to the liver, a CETP-independent m-RCT path exists, in which LDL mediates the transfer of cholesterol from macrophages to feces. Graphical Abstract: A graphical abstract is available for this article.

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Mazière, J. C., C. Mazière, S. Emami, B. Noel, Y. Poumay, M. F. Ronveaux, E. Chastre, et al. "Processing and characterization of the low density lipoprotein receptor in the human colonic carcinoma cell subclone HT29-18: A potential pathway for delivering therapeutic drugs and genes." Bioscience Reports 12, no. 6 (December 1, 1992): 483–94. http://dx.doi.org/10.1007/bf01122036.

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Low density lipoprotein (LDL) processing has been investigated in the subcloned human colonic carcinoma cell line HT29-18. LDL binding at 4°C was a saturable process in relation to time and LDL concentration. The Kd for LDL binding was 11 μg/ml. ApoE-free HDL3 or acetylated LDL did not significantly compete with125I-LDL binding, up to 500 μg/ml.125I-LDL binding was decreased by 70% in HT29-18 cells preincubated for 24 hours in culture medium containing 100 μg/ml unlabelled LDL. Ligand blotting studies performed on HT29-18 homogenates using colloidal gold labelled LDL indicated the presence of one autoradiographic band corresponding to an apparent molecular weight of 130 kDa, which is consistent with the previously reported molecular weight of the LDL receptor in human fibroblasts. At 37°C,125I-LDL was actively internalized by HT29-18 cells and lysosomal degradation occurred as demonstrated by the inhibitory effect of chloroquine. LDL uptake and degradation by HT29-18 cells also resulted in a marked decrease in endogenous sterol synthesis. These data demonstrate that the HT29-18 human cancerous intestinal cells are able to specifically bind and internalize LDL, and that LDL processing results in down-regulation of sterol biosynthesis. Thus, intestinal epithelial cells possess specific LDL receptors that can be exploited to accomplish drug delivery and gene transfer via the receptor-mediated endocytosis pathway.

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Levels, J. H. M., J. A. Marquart, P. R. Abraham, A. E. van den Ende, H. O. F. Molhuizen, S. J. H. van Deventer, and J. C. M. Meijers. "Lipopolysaccharide Is Transferred from High-Density to Low-Density Lipoproteins by Lipopolysaccharide-Binding Protein and Phospholipid Transfer Protein." Infection and Immunity 73, no. 4 (April 2005): 2321–26. http://dx.doi.org/10.1128/iai.73.4.2321-2326.2005.

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ABSTRACT Lipopolysaccharide (LPS), the major outer membrane component of gram-negative bacteria, is a potent endotoxin that triggers cytokine-mediated systemic inflammatory responses in the host. Plasma lipoproteins are capable of LPS sequestration, thereby attenuating the host response to infection, but ensuing dyslipidemia severely compromises this host defense mechanism. We have recently reported that Escherichia coli J5 and Re595 LPS chemotypes that contain relatively short O-antigen polysaccharide side chains are efficiently redistributed from high-density lipoproteins (HDL) to other lipoprotein subclasses in normal human whole blood (ex vivo). In this study, we examined the role of the acute-phase proteins LPS-binding protein (LBP) and phospholipid transfer protein (PLTP) in this process. By the use of isolated HDL containing fluorescent J5 LPS, the redistribution of endotoxin among the major lipoprotein subclasses in a model system was determined by gel permeation chromatography. The kinetics of LPS and lipid particle interactions were determined by using Biacore analysis. LBP and PLTP were found to transfer LPS from HDL predominantly to low-density lipoproteins (LDL), in a time- and dose-dependent manner, to induce remodeling of HDL into two subpopulations as a consequence of the LPS transfer and to enhance the steady-state association of LDL with HDL in a dose-dependent fashion. The presence of LPS on HDL further enhanced LBP-dependent interactions of LDL with HDL and increased the stability of the HDL-LDL complexes. We postulate that HDL remodeling induced by LBP- and PLTP-mediated LPS transfer may contribute to the plasma lipoprotein dyslipidemia characteristic of the acute-phase response to infection.

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Pincinato, Eder de Carvalho, Patricia Moriel, and Dulcinéia Saes Parra Abdalla. "Cholesterol oxides inhibit cholesterol esterification by lecithin: cholesterol acyl transferase." Brazilian Journal of Pharmaceutical Sciences 45, no. 3 (September 2009): 429–35. http://dx.doi.org/10.1590/s1984-82502009000300007.

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Cholesterol oxides are atherogenic and can affect the activity of diverse important enzymes for the lipidic metabolism. The effect of 7β-hydroxycholesterol, 7-ketocholesterol, 25-hydroxycholesterol, cholestan-3β,5α,6β-triol,5,6β-epoxycholesterol, 5,6α-epoxycholesterol and 7α-hydroxycholesterol on esterification of cholesterol by lecithin:cholesterol acyl transferase (LCAT, EC 2.3.1.43) and the transfer of esters of cholesterol oxides from high density lipoprotein (HDL) to low density lipoproteins (LDL) and very low density lipoproteins (VLDL) by cholesteryl ester transfer protein (CETP) was investigated. HDL enriched with increasing concentrations of cholesterol oxides was incubated with fresh plasma as source of LCAT. Cholesterol and cholesterol oxides esterification was followed by measuring the consumption of respective free sterol and oxysterols. Measurements of cholesterol and cholesterol oxides were done by gas-chromatography. 14C-cholesterol oxides were incorporated into HDL2 and HDL3 subfractions and then incubated with fresh plasma containing LCAT and CETP. The transfer of cholesterol oxide esters was followed by measuring the 14C-cholesterol oxide-derived esters transferred to LDL and VLDL. All the cholesterol oxides studied were esterified by LCAT after incorporation into HDL particles, competing with cholesterol by LCAT. Cholesterol esterification by LCAT was inversely related to the cholesterol oxide concentration. The esterification of 14C-cholesterol oxides was higher in HDL3 and the transfer of the derived esters was greater from HDL2 to LDL and VLDL. The results suggest that cholesterol esterification by LCAT is inhibited in cholesterol oxide-enriched HDL particles. Moreover, the cholesterol oxides-derived esters are efficiently transferred to LDL and VLDL. Therefore, we suggest that cholesterol oxides may exert part of their atherogenic effect by inhibiting cholesterol esterification on the HDL surface and thereby disturbing reverse cholesterol transport.

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Aslan, Mutay, Filiz Ozcan, and Ertan Kucuksayan. "Increased Small Dense LDL and Decreased Paraoxonase Enzyme Activity Reveals Formation of an Atherogenic Risk in Streptozotocin-Induced Diabetic Guinea Pigs." Journal of Diabetes Research 2013 (2013): 1–8. http://dx.doi.org/10.1155/2013/860190.

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This study aimed to investigate LDL subfraction distribution as well as serum cholesteryl ester transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT), and paraoxonase (PON1) activity in streptozotocin-induced diabetic guinea pigs.Materials/Methods. Guinea pigs were given a single intraperitoneal (ip) injection of streptozotocin (STZ) and animals having fasting blood glucose levels greater than 200 mg/dl, were considered diabetic. Protein levels of LCAT and CETP were determined via ELISA. Paraoxonase activity was measured kinetically by the formation of phenol while LDL subfraction analysis was done by disc polyacrylamide gel electrophoresis.Results. Plasma glucose and high-density lipoprotein (HDL) cholesterol were significantly increased while total cholesterol and LDL cholesterol were significantly decreased in diabetic guinea pigs compared to controls. LDL subfraction analysis revealed a significant decrease in nonatherogenic LDL-2 subfraction and a significant increase in atherogenic LDL-4 subfraction in diabetic guinea pigs compared to controls. Plasma CETP and PON1 levels were significantly decreased while LCAT showed no significant difference in diabetic guinea pigs compared to controls.Conclusion. Decreased non-atherogenic LDL-1, LDL-2 subfractions, increased small dense LDL-4 subfraction, and decreased PON1 activity, reveals formation of an atherogenic risk in diabetic guinea pigs. Decrease in CETP levels supports the observed increase in HDL cholesterol levels in diabetic guinea pigs.

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Yoshino, Gen, and George Steiner. "Transfer of newly made triglyceride from hepatocytes to preexisting extracellular very low density lipoproteins." Canadian Journal of Physiology and Pharmacology 65, no. 3 (March 1, 1987): 337–43. http://dx.doi.org/10.1139/y87-058.

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Previous in vivo studies suggested a new model to describe the metabolism of very low density lipoproteins (VLDL). It was hypothesized that some of the lipoprotein triglyceride was transferred directly from hepatocytes and intestinal mucosal cells into preexisting extracellular VLDL particles. These studies employ an in vitro system to test this hypothesis. Isolated rat liver cells containing newly made radioactive triglyceride were prepared. These cells were incubated in medium to which exogenous VLDL had or had not been added. The presence of extracellular VLDL (rat or human) stimulated the transfer of labeled triglyceride out of the liver cells. This triglyceride was recovered in the medium's VLDL (as determined by its density and its precipitability by MnCl2–heparin or by anti-apoprotein B). Although these studies focussed on VLDL, preliminary data showed that similar triglyceride transfer occurred in the presence of the other apoprotein B containing lipoprotein, low density lipoprotein (LDL). However, in the presence of equivalent amounts of LDL, this triglyceride transfer was less than that seen in the presence of exogenous VLDL. Furthermore, the increased triglyceride released in the presence of LDL occurred entirely in the d < 1.006 fraction of the medium. That released in the presence of VLDL was recovered in the d > 1.006 fraction. Hence, we conclude that the transfer of the newly made triglyceride was from the cell to the extracellular lipoprotein that had been added to the medium. The transfer of triglyceride to VLDL did not depend on the synthesis and release of new VLDL particles because it was not accompanied by a change in the production of [14C]leucine VLDL protein, it was not blocked by chloroquine, and the LDL induced triglyceride release occurred into the d > 1.006 fraction. This transfer did not depend on the previously described triglyceride-transfer factor. The present in vitro studies support the model suggested by our earlier in vivo studies. The VLDL particle does not appear to be metabolized as a complete intact unit. Rather, some of its major lipid component, triglyceride, can move directly into and out of already existing extracellular lipoproteins.

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So, Jisun, Bela Asztalos, Katalin Horvath, Alice Lichtenstein, and Stefania Lamon-Fava. "EPA and DHA Have Differential Effects on Cholesterol Ester Transfer Protein and Lipoprotein Lipase Activities Following Plasma Triglycerides Lowering." Current Developments in Nutrition 4, Supplement_2 (May 29, 2020): 662. http://dx.doi.org/10.1093/cdn/nzaa049_055.

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Abstract Objectives Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are effective in reducing plasma triglyceride (TG) concentrations but have divergent effects on LDL cholesterol (LDL-C) concentrations. Differential regulations of cholesterol ester transfer protein (CETP) and lipoprotein lipase (LPL) activities are possible mechanisms of their differential effects. We assessed the effects of EPA and DHA supplementation on plasma lipid profiles and two enzyme activities involved in lipoprotein metabolism. Methods Nine men and twelve postmenopausal women (N = 21, 50–75y) with chronic inflammation (CRP > 2 mg/L) were enrolled in a randomized, double-blind, crossover trial consisting of a 4-wk lead-in phase with high oleic acid sunflower oil (3 g/d) followed by two 10-wk EPA and DHA supplementation phases (3 g/d each) separated by a 10-wk washout phase. Plasma was collected after the lead-in (baseline) and each n-3 fatty acid supplementation phase for analysis of TG, total cholesterol and HDL-C, and CETP and post-heparin LPL activities. LDL-C was estimated using the Friedewald formula. Results Subjects were recruited to have moderately elevated TG and LDL-C concentrations (mean ± SEM: 141 ± 11 and 130 ± 6 mg/dL, respectively). Compared to baseline, EPA supplementation lowered TG concentration (−28 ± 6 mg/dL, P < 0.001) and CETP activity (−1.6 ± 1.1 µg/mL/h, P < 0.05), whereas LDL-C concentration and LPL activity were unchanged. The changes in TG concentration and CETP activity were negatively correlated with baseline TG (r = −0.77 and −0.45, respectively, both P < 0.05). DHA supplementation lowered TG concentration (−31 ± 8 mg/dL, P < 0.001), and increased LDL-C concentration (+10 ± 4 mg/dL, P < 0.01) and LPL activity (+6.1 ± 4.0 mU/mL, P < 0.03), CETP activity was unchanged. The DHA-mediated increase in LPL activity was correlated with the baseline TG concentration and change in TG concentration (r = 0.64 and ρ = −0.45, respectively, both P < 0.05). Conclusions In the context of the established TG-lowering effects of EPA and DHA, these n-3 fatty acids affected CETP and LPL activities differently. DHA-induced change in LDL-C concentration may be related to increased LPL activity, and the conversion of very low-density lipoprotein to LDL. Funding Sources AFRI/NIFA; USDA.

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Wade, D. P., B. L. Knight, and A. K. Soutar. "Detection of the low-density-lipoprotein receptor with biotin-low-density lipoprotein. A rapid new method for ligand blotting." Biochemical Journal 229, no. 3 (August 1, 1985): 785–90. http://dx.doi.org/10.1042/bj2290785.

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A new technique has been developed to identify low-density-lipoprotein (LDL) receptors on nitrocellulose membranes, after transfer from SDS/polyacrylamide gels, by ligand blotting with biotin-modified LDL. Modification with biotin hydrazide of periodate-oxidized lipoprotein sugar residues does not affect the ability of the lipoprotein to bind to the LDL receptor. Bound lipoprotein is detected with high sensitivity by a streptavidin-biotin-peroxidase complex, and thus this method eliminates the need for specific antibodies directed against the ligand. The density of the bands obtained is proportional to the amount of pure LDL receptor protein applied to the SDS/polyacrylamide gel, so that it is possible to quantify LDL receptor protein in cell extracts. Biotin can be attached to other lipoproteins, for example very-low-density lipoproteins with beta-mobility, and thus the method will be useful in the identification and isolation of other lipoprotein receptors.

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Castilho, Lucia N., Helena C. F. Oliveira, Patrı́cia M. Cazita, Admar C. de Oliveira, Antonio Sesso, and Eder C. R. Quintão. "Oxidation of LDL enhances the cholesteryl ester transfer protein (CETP)-mediated cholesteryl ester transfer rate to HDL, bringing on a diminished net transfer of cholesteryl ester from HDL to oxidized LDL." Clinica Chimica Acta 304, no. 1-2 (February 2001): 99–106. http://dx.doi.org/10.1016/s0009-8981(00)00401-0.

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SAKAI, N., S. YAMASHITA, K. I. HIRANO, M. ISHIGAMI, T. ARAI, K. KOBAYASHI, T. FUNAHASHI, and Y. MATSUZAWA. "Decreased affinity of low density lipoprotein (LDL) particles for LDL receptors in patients with cholesteryl ester transfer protein deficiency." European Journal of Clinical Investigation 25, no. 5 (May 1995): 332–39. http://dx.doi.org/10.1111/j.1365-2362.1995.tb01710.x.

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Iwata, Seiji, Nagahiko Sakuma, Takeshi Hibino, Takaaki Sato, Akihiko Yoneyama, Yoshinobu Kamiya, Masanobu Kawaguchi, Takao Fujinami, and Mitoshi Kunimatsu. "Influence of anti-LDL receptor antibody on the transfer of cholesterol from LDL to isolated lymphocytes in normal subjects." Clinical Biochemistry 28, no. 3 (June 1995): 309–11. http://dx.doi.org/10.1016/0009-9120(94)00070-c.

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Wu, Huimin, Fei Fang, Chengcheng Wang, Xiao Hong, Dajing Chen, and Xiaojun Huang. "Selective Molecular Recognition of Low Density Lipoprotein Based on β-Cyclodextrin Coated Electrochemical Biosensor." Biosensors 11, no. 7 (June 30, 2021): 216. http://dx.doi.org/10.3390/bios11070216.

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The excess of low-density lipoprotein (LDL) strongly promotes the accumulation of cholesterol on the arterial wall, which can easily lead to the atherosclerotic cardiovascular diseases (ACDs). It is a challenge on how to recognize and quantify the LDL with a simple and sensitive analytical technology. Herein, β-cyclodextrins (β-CDs), acting as molecular receptors, can bind with LDL to form stable inclusion complexes via the multiple interactions, including electrostatic, van der Waals forces, hydrogen bonding and hydrophobic interactions. With the combination of gold nanoparticles (Au NPs) and β-CDs, we developed an electrochemical sensor providing an excellent molecular recognition and sensing performance towards LDL detection. The LDL dynamic adsorption behavior on the surface of the β-CD-Au electrode was explored by electrochemical impedance spectroscopy (EIS), displaying that the electron-transfer resistance (Ret) values were proportional to the LDL (positively charged apolipoprotein B-100) concentrations. The β-CD-Au modified sensor exhibited a high selectivity and sensitivity (978 kΩ·µM−1) toward LDL, especially in ultra-low concentrations compared with the common interferers HDL and HSA. Due to its excellent molecular recognition performance, β-CD-Au can be used as a sensing material to monitor LDL in human blood for preventing ACDs in the future.

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Sawada, Naoko, Takashi Obama, Mirei Mizuno, Kiyoshi Fukuhara, Sanju Iwamoto, Toshihiro Aiuchi, Tomohiko Makiyama, and Hiroyuki Itabe. "Transfer and Enzyme-Mediated Metabolism of Oxidized Phosphatidylcholine and Lysophosphatidylcholine between Low- and High-Density Lipoproteins." Antioxidants 9, no. 11 (October 26, 2020): 1045. http://dx.doi.org/10.3390/antiox9111045.

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Oxidized low-density lipoprotein (oxLDL) and oxidized high-density lipoprotein (oxHDL), known as risk factors for cardiovascular disease, have been observed in plasma and atheromatous plaques. In a previous study, the content of oxidized phosphatidylcholine (oxPC) and lysophosphatidylcholine (lysoPC) species stayed constant in isolated in vivo oxLDL but increased in copper-induced oxLDL in vitro. In this study, we prepared synthetic deuterium-labeled 1-palmitoyl lysoPC and palmitoyl-glutaroyl PC (PGPC), a short chain-oxPC to elucidate the metabolic fate of oxPC and lysoPC in oxLDL in the presence of HDL. When LDL preloaded with d13-lysoPC was mixed with HDL, d13-lysoPC was recovered in both the LDL and HDL fractions equally. d13-LysoPC decreased by 50% after 4 h of incubation, while d13-PC increased in both fractions. Diacyl-PC production was abolished by an inhibitor of lecithin-cholesterol acyltransferase (LCAT). When d13-PGPC-preloaded LDL was incubated with HDL, d13-PGPC was transferred to HDL in a dose-dependent manner when both LCAT and lipoprotein-associated phospholipase A2 (Lp-PLA2) were inhibited. Lp-PLA2 in both HDL and LDL was responsible for the hydrolysis of d13-PGPC. These results suggest that short chain-oxPC and lysoPC can transfer between lipoproteins quickly and can be enzymatically converted from oxPC to lysoPC and from lysoPC to diacyl-PC in the presence of HDL.

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Kosmas, Constantine E., Eddy Dejesus, Digna Rosario, and Timothy J. Vittorio. "CETP Inhibition: Past Failures and Future Hopes." Clinical Medicine Insights: Cardiology 10 (January 2016): CMC.S32667. http://dx.doi.org/10.4137/cmc.s32667.

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The atheroprotective role of high-density lipoprotein cholesterol (HDL-C) in cardiovascular disease has been unequivocally established, and epidemiological data have clearly demonstrated a strong inverse relationship between HDL-C levels and the risk of cardiovascular events, which is independent of the low-density lipoprotein cholesterol (LDL-C) levels. Thus, it would be logical to hypothesize that raising HDL-C might potentially lead to a reduction of cardiovascular risk. Cholesteryl ester transfer protein (CETP) promotes the transfer of cholesteryl esters from HDL to very low-density lipoprotein and LDL. Therefore, CETP inhibition raises HDL-C levels and decreases LDL-C levels. The first trials with CETP inhibitors failed to show a reduction in cardiovascular events. However, newer CETP inhibitors with more favorable effects on lipids are presently being tested in clinical trials with the hope that their use may lead to a reduction in cardiovascular risk. This review aims to provide the current evidence regarding CETP inhibition, as well as the clinical and scientific data pertaining to the new CETP inhibitors in development.

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Littmann, Karin, Karolina Szummer, Hannes Hagström, Karoly Dolapcsiev, Jonas Brinck, and Mats Eriksson. "Lomitapide treatment in a female with homozygous familial hypercholesterolaemia: a case report." European Heart Journal - Case Reports 4, no. 1 (February 1, 2020): 1–6. http://dx.doi.org/10.1093/ehjcr/ytaa020.

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Abstract Background Homozygous familial hypercholesterolaemia (FH) is an autosomal-dominant inherited disease presenting with highly elevated low-density lipoprotein cholesterol (LDL-C) levels. Untreated, the patient can develop atherosclerosis and cardiovascular disease already in adolescence. Treatment with statins and ezetimibe is usually not sufficient and LDL apheresis is often required. Lomitapide, an inhibitor of the microsomal triglyceride transfer protein, reduces LDL-C and triglyceride levels and can be used alone or in combination with other therapies in homozygous FH. However, experience with this agent is still limited. Case summary We present a young female who was diagnosed with homozygous FH at 6 years of age. She shows a complete lack of normal LDL receptor activity and no cholesterol-lowering effect from statins. The patient was treated with LDL apheresis from 7 years of age. When LDL apheresis treatment extended to twice a week, she began to experience adverse effects, including catheter-related complications, infections, and hospital admissions. When lomitapide treatment was initiated, the frequency of apheresis reduced, the LDL-C levels improved and she has not had any further hospital admissions since. Initially, she suffered from gastrointestinal disturbances. However, after 3 years of treatment with lomitapide 20 mg/day, the patient has not experienced any adverse effects. Discussion In this female with homozygous FH adding lomitapide treatment to LDL apheresis has contributed to improved LDL-C levels, a reduction in LDL apheresis sessions and enhanced quality of life. No adverse effects have been reported. These findings suggest that lomitapide can be a drug of choice in patients with homozygous FH.

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Itabe, Hiroyuki, Rina Kato, Naoko Sawada, Takashi Obama, and Matsuo Yamamoto. "The Significance of Oxidized Low-Density Lipoprotein in Body Fluids as a Marker Related to Diseased Conditions." Current Medicinal Chemistry 26, no. 9 (May 21, 2019): 1576–93. http://dx.doi.org/10.2174/0929867325666180307114855.

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Oxidatively modified low-density lipoprotein (oxLDL) is known to be involved in various diseases, including cardiovascular diseases. The presence of oxLDL in the human circulatory system and in atherosclerotic lesions has been demonstrated using monoclonal antibodies. Studies have shown the significance of circulating oxLDL in various systemic diseases, including acute myocardial infarction and diabetic mellitus. Several different enzyme-linked immunosorbent assay (ELISA) procedures to measure oxLDL were utilized. Evidence has been accumulating that reveals changes in oxLDL levels under certain pathological conditions. Since oxLDL concentration tends to correlate with low-density lipoprotein (LDL)-cholesterol, the ratio of ox-LDL and LDL rather than oxLDL concentration alone has also been focused. In addition to circulating plasma, LDL and oxLDL are found in gingival crevicular fluid (GCF), where the ratio of oxLDL to LDL in GCF is much higher than in plasma. LDL and oxLDL levels in GCF show an increase in diabetic patients and periodontal patients, suggesting that GCF might be useful in examining systemic conditions. GCF oxLDL increased when the teeth were affected by periodontitis. It is likely that oxLDL levels in plasma and GCF could reflect oxidative stress and transfer efficacy in the circulatory system.

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Hu, Jerry, and Scot Walker. "Cholesterol Ester Transfer Protein Inhibitor Review." Hospital Pharmacy 52, no. 9 (September 11, 2017): 596–98. http://dx.doi.org/10.1177/0018578717729669.

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Treatment of blood cholesterol is part of a strategy to lower atherosclerotic cardiovascular (ASCVD) risk. While use of HMG-CoA reductase inhibitors to modify cholesterol levels is the primary means of lowering the risk of an ASCVD event, residual risk remains. A new strategy being investigated is the use of cholesterol ester transfer protein (CETP) inhibitors to raise the levels of high-density lipoprotein cholesterol (HDL-C) and lower low-density lipoprotein cholesterol (LDL-C). While initial large-scale studies demonstrated no reduction of cardiovascular events, one CETP inhibitor, anacetrapib, has demonstrated a reduction in cardiovascular events in the REVEAL trial.

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Skeggs, Josephine W., and Richard E. Morton. "LDL and HDL enriched in triglyceride promote abnormal cholesterol transport." Journal of Lipid Research 43, no. 8 (August 2002): 1264–74. http://dx.doi.org/10.1194/jlr.m100431-jlr200.

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Hypertriglyceridemia induces multiple changes in lipoprotein composition. Here we investigate how one of these modifications, triglyceride (TG) enrichment, affects HDL and LDL function when this alteration occurs under conditions in which more polar components can naturally re-equilibrate. TG-enriched lipoproteins were produced by co-incubating VLDL, LDL, and HDL with cholesteryl ester (CE) transfer protein. The resulting 2.5-fold increase in TG/CE ratio did not measurably alter the apoprotein composition of LDL or HDL, or modify LDL size. HDL mean diameter increased slightly from 9.1 to 9.4 nm. Modified LDL was internalized by fibroblasts normally, but its protein was degraded much less efficiently. This likely reflects an aberrant apolipoprotein B (apoB) conformation, as suggested by its resistance to V8 protease digestion and altered LDL electrophoretic mobility. TG-enriched LDL ineffectively down-regulated cholesterol biosynthesis compared with control LDL at the same protein concentration, but was equivalent in sterol regulation when compared on a cholesterol basis. TG-enriched HDL promoted greater net cholesterol efflux from cholesterol-loaded J774 cells. However, cholesterol associated with TG-enriched HDL was inefficiently esterified by lecithin:cholesterol acyltransferase, and TG-enriched HDLs were poor donors of CE to HepG2 hepatocytes by selective uptake.We conclude that TG-enrichment, in the absence of other significant alterations in lipoprotein composition, is sufficient to alter both cholesterol delivery and removal mechanisms. Some of these abnormalities may contribute to increased coronary disease in hypertriglyceridemia.

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Dashty, Monireh, Mohammad Motazacker, Johannes Levels, Marcel de Vries, Morteza Mahmoudi, Maikel Peppelenbosch, and Farhad Rezaee. "Proteome of human plasma very low-density lipoprotein and low-density lipoprotein exhibits a link with coagulation and lipid metabolism." Thrombosis and Haemostasis 111, no. 03 (2014): 518–30. http://dx.doi.org/10.1160/th13-02-0178.

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SummaryApart from transporting lipids through the body, the human plasma lipoproteins very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) are also thought to serve as a modality for intra-organismal protein transfer, shipping proteins with important roles in inflammation and thrombosis from the site of synthesis to effector locations. To better understand the role of VLDL and LDL in the transport of proteins, we applied a combination of LTQ ORBITRAP-XL (nLC-MS/MS) with both in-SDS-PAGE gel and in-solution tryptic digestion of pure and defined VLDL and LDL fractions. We identified the presence of 95 VLDL-and 51 LDL-associated proteins including all known apolipoproteins and lipid transport proteins, and intriguingly a set of coagulation proteins, complement system and anti-microbial proteins. Prothrombin, protein S, fibrinogen γ, PLTP, CETP, CD14 and LBP were present on VLDL but not on LDL. Prenylcysteine oxidase 1, dermcidin, cathelicidin antimicrobial peptide, TFPI-1 and fibrinogen α chain were associated with both VLDL and LDL. Apo A-V is only present on VLDL and not on LDL. Collectively, this study provides a wealth of knowledge on the protein constituents of the human plasma lipoprotein system and strongly supports the notion that protein shuttling through this system is involved in the regulation of biological processes. Human diseases related to proteins carried by VLDL and LDL can be divided in three major categories: 1 – dyslipidaemia, 2 – atherosclerosis and vascular disease, and 3 – coagulation disorders.

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Nguyen, Mai K. L., Jaimy Jose, Mohamed Wahba, Marc Bernaus-Esqué, Andrew J. Hoy, Carlos Enrich, Carles Rentero, and Thomas Grewal. "Linking Late Endosomal Cholesterol with Cancer Progression and Anticancer Drug Resistance." International Journal of Molecular Sciences 23, no. 13 (June 29, 2022): 7206. http://dx.doi.org/10.3390/ijms23137206.

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Cancer cells undergo drastic metabolic adaptions to cover increased bioenergetic needs, contributing to resistance to therapies. This includes a higher demand for cholesterol, which often coincides with elevated cholesterol uptake from low-density lipoproteins (LDL) and overexpression of the LDL receptor in many cancers. This implies the need for cancer cells to accommodate an increased delivery of LDL along the endocytic pathway to late endosomes/lysosomes (LE/Lys), providing a rapid and effective distribution of LDL-derived cholesterol from LE/Lys to other organelles for cholesterol to foster cancer growth and spread. LDL-cholesterol exported from LE/Lys is facilitated by Niemann–Pick Type C1/2 (NPC1/2) proteins, members of the steroidogenic acute regulatory-related lipid transfer domain (StARD) and oxysterol-binding protein (OSBP) families. In addition, lysosomal membrane proteins, small Rab GTPases as well as scaffolding proteins, including annexin A6 (AnxA6), contribute to regulating cholesterol egress from LE/Lys. Here, we summarize current knowledge that links upregulated activity and expression of cholesterol transporters and related proteins in LE/Lys with cancer growth, progression and treatment outcomes. Several mechanisms on how cellular distribution of LDL-derived cholesterol from LE/Lys influences cancer cell behavior are reviewed, some of those providing opportunities for treatment strategies to reduce cancer progression and anticancer drug resistance.

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Hogue, Jean-Charles, Benoît Lamarche, Daniel Gaudet, Mathieu Larivière, André J. Tremblay, Jean Bergeron, Isabelle Lemieux, Jean-Pierre Després, Claude Gagné, and Patrick Couture. "Relationship between cholesteryl ester transfer protein and LDL heterogeneity in familial hypercholesterolemia." Journal of Lipid Research 45, no. 6 (March 16, 2004): 1077–83. http://dx.doi.org/10.1194/jlr.m300420-jlr200.

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Chana, Ravinder S., W. Dale Treleaven, Robert J. Cushley, and Urs P. Steinbrecher. "Dynamic structure of the lower density lipoproteins. I. Incorporation of high levels of labelled lipids into very low and low density lipoproteins." Biochemistry and Cell Biology 68, no. 1 (January 1, 1990): 180–88. http://dx.doi.org/10.1139/o90-024.

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Selectively labelled lipids have been incorporated into the surface monolayer of human serum low density lipoprotein (LDL) and very low density lipoprotein (VLDL). From 3 to 17 mol% of phosphatidylcholine, selectively deuterated at various positions along the sn-2-acyl chain, was transferred from unilamellar vesicles to VLDL using a partially purified phosphatidylcholine transfer protein. Selectively deuterated palmitic acids were incorporated into LDL (6–20 mol%) and into VLDL (7–10 mol%). Electron microscopy, light scattering, and 31P nuclear magnetic resonance indicated that particle size remained unchanged. Gel exclusion chromatography and chemical analysis showed no difference in hydrodynamic properties and only slight alteration to particle component ratios. Biological activity of labelled VLDL was measured from the rate of cholesterol esterification by cultured J774A.1 cells. Effect of labelling LDL was evaluated by monitoring LDL uptake and degradation by cultured human skin fibroblasts. In all cases the lipoproteins containing labels were indistinguishable from their native counterparts.Key words: deuterium incorporation, cell culture studies, light scattering, lipoproteins, electron microscopy.

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Maldar, Shadab B., and Christopher Jude Pinto. "Homozygous familial hypercholesterolaemia in a patient presenting with hypertensive encephalopathy." BMJ Case Reports 15, no. 10 (October 2022): e250265. http://dx.doi.org/10.1136/bcr-2022-250265.

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Homozygous familial hypercholesterolaemia (HoFH) is a disorder affecting low-density lipoprotein (LDL) receptor genes. Patients typically have a triad of elevated LDL-cholesterol (LDL-C), xanthomatosis and premature atherosclerotic cardiovascular disease. Our patient, a preteen boy, presented with signs of hypertensive encephalopathy. Physical examination showed arcus cornealis, planar xanthomas and tuberous xanthomas. After appropriate investigations, a direct aetiology of the hypertension could not be elucidated; however, our patient’s hypertension resolved with the reduction in serum lipid levels. β-hydroxy β-methylglutaryl coenzyme A reductase and cholesterol absorption inhibitors were administered as first-line treatment. A significant proportion of patients with HoFH continue to have elevated LDL-C levels, thereby requiring second-line agents, such as proprotein convertase subtilisin/kexin type inhibitors (evolocumab), microsomal triglyceride transfer protein inhibitors (lomitapide) and angiopoietin-like protein inhibitors (evinacumab). This case report aimed to raise awareness among paediatricians to consider HoFH as a possible aetiology in a child presenting with hypertension and suggestive physical findings.

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Arnesen, Arne M., Morten Halvorsen, and Kjell J. Nilssen. "Development of Hypoosmoregulatory Capacity in Arctic char (Salvelinus alpinus) Reared under either Continuous Light or Natural Photoperiod." Canadian Journal of Fisheries and Aquatic Sciences 49, no. 2 (February 1, 1992): 229–37. http://dx.doi.org/10.1139/f92-027.

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Two groups of Arctic char (Salvelinus alpinus) were reared in freshwater (5–6 °C) under either continuous light (LDL) from first feeding (March) or LDL until July and then natural photoperiod (NDL, 70°N). Direct transfer to seawater (5.5 °C, 35 ppt) in February resulted in both groups exhibiting increases in blood plasma osmolality, Na+, and Mg2+ concentrations and a significant decrease in muscle water content. When tested in May, an improvement in seawater tolerance was evident in both groups. In June, only the NDL fish showed further improvements in hypoosmoregulatory capacity, since they exhibited only minor fluctuations in plasma constituents and muscle water content following direct transfer to seawater. Increased body size could partially explain the improved seawater tolerance in the experimental groups. Acclimation to brackish water prior to transfer to 35 ppt seawater in June improved seawater tolerance only in fish reared under continuous light. The results indicate that the seasonal increase in photoperiod stimulates the development of hypoosmoregulatory capacity whilst the fish are still resident in freshwater.

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As'ari, Hasyim. "Decrease of LDL Cholesterol through Increase of HDL Cholesterol by Administering Garcinia mangostana L. Peel Extract in White Mice." Folia Medica Indonesiana 57, no. 4 (December 7, 2021): 298. http://dx.doi.org/10.20473/fmi.v57i4.23728.

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Highlight:Ethanol extract of Garcinia mangostana L. peel reduce malondialdehyde.Garcinia mangostana L. peel extract can increase non-radical products which impact in decreasing LDL cholesterol and increasing HDL cholesterol. Abstract:Atherosclerosis contributes to coronary heart disease which may lead to fatality. High cholesterol consumption, stress, and smoking can increase LDL cholesterol in the blood. Consumption of unsaturated fats, high fiber foods, exercise, quitting smoking, losing weight, and giving hypolipidemic drugs, especially herbs, can increase HDL cholesterol and decrease LDL cholesterol. Garcinia mangostana L. peel extract can decrease LDL cholesterol by increasing reverse HDL cholesterol transport to the liver. The study used post test control group design. This study was experimental laboratory research with population of hypercholesterolemic male white mice aged 3-4 weeks with 100-200 grams weight. The HDL and LDL cholesterol data were collected through an enzymatic method by spectrophotometer. This study used analysis of variance (Anova) with significance level of α <0.05. The experiment divided the subjects into positive and negative control groups with dosage variations of 50, 150, 250, and 350 mg/kgBW. Examination of hypercholesterolemia in white mice was conducted on the 8th day. The examination of HDL and LDL cholesterol given peel extract of Garcinia mangostana L. was conducted on the 22nd day. The analysis showed that giving Garcinia mangostana L. peel extract for various dosages could significantly decrease LDL cholesterol and increase HDL cholesterol (p <0.05). Peel extract of Garcinia mangostana L. that contained mangosteen could increase non-radical products that could prevent the transfer of ester cholesterol from HDL to VLDL which impact in increasing HDL cholesterol and decreasing LDL cholesterol.

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Goldberg, I. J., R. S. Rosenfeld, I. Paul, and B. Leeman. "Generation of plasma free cholesterol from circulating lipoprotein-associated cholesteryl ester." American Journal of Physiology-Endocrinology and Metabolism 250, no. 3 (March 1, 1986): E265—E268. http://dx.doi.org/10.1152/ajpendo.1986.250.3.e265.

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Studies were performed to investigate the contribution of lipoprotein-associated cholesteryl ester (CE) in the monkey to circulating free cholesterol (FC). Monkey plasma was incubated with [14C]- or [3H]cholesteryl ester, and radiolabeled low-density lipoproteins (LDL) and high-density lipoproteins (HDL) were isolated by ultracentrifugation. Animals received labeled LDL or HDL. A rapid transfer of CE between lipoproteins was observed, consistent with an active CE transfer protein activity in the monkey. Within 4 h the percent of plasma radioactivity in FC after injection of CE-labeled LDL or HDL was, respectively, 30 and 7% of that of the ester. To determine whether the generation of FC was due to a circulating plasma cholesteryl ester hydrolase, monkey plasma was incubated with CE-labeled lipoproteins with and without 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB). A small amount of FC (less than 3% of the radioactivity) was generated during this incubation but most of the FC production was inhibited by DTNB. Although a small amount of FC can be produced by a plasma cholesteryl esterase (perhaps via reverse action of lecithin-cholesterol acyltransferase), most of the FC in plasma derived from lipoprotein-associated CE is probably due to tissue uptake of lipoproteins and subsequent intracellular hydrolysis of the CE to produce FC.

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Rochester, Charmaine D., and Catherine E. Cooke. "The Changing Face of Dyslipidemia Therapies." Journal of Pharmacy Practice 19, no. 2 (April 2006): 79–93. http://dx.doi.org/10.1177/0897190006290137.

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To date, the major emphasis of dyslipidemia management has focused on the reduction of serum low-density lipoprotein cholesterol (LDL-C) levels, which several robust trials show significantly decreases the risk of coronory heart disease (CHD). To achieve goal LDL-C levels will require that some individuals take more than 1 cholesterol-lowering medication. In addition, many dyslipidemic patients also have concomitant risk factors for cardiovascular disease including hypertension, elevated plasma glucose, and high body mass index, requiring additional therapies. In addition to drugs that lower LDL-C, several agents under investigation are targeting other markers for decreasing the risk of atherosclerotic disease. Some of these agents target the reduction of C-reactive protein with a more potent statin, increased high-density lipoprotein cholesterol (HDL-C) with the cholesterol ester transfer protein inhibitor, inhibition of triglyceride or very-low-density lipoprotein cholesterol (VLDL-C) with the acyl coenzyme A: cholesterol acyltransferase inhibitor, reduction of VLDL-C with microsomal triglyceride transfer protein inhibitor, change in percentage coronary atheroma volume with HDL-C mimetics, and the reduction of bile acid transport and reabsorption with the ileal bile acid transport inhibitors. This review will provide an overview of the existing landscape for the medical treatment of dyslipidemia, including available therapies and future trends.

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Purnell, Jonathan Q., Steven E. Kahn, John J. Albers, David N. Nevin, John D. Brunzell, and Robert S. Schwartz. "Effect of Weight Loss with Reduction of Intra-Abdominal Fat on Lipid Metabolism in Older Men*." Journal of Clinical Endocrinology & Metabolism 85, no. 3 (March 1, 2000): 977–82. http://dx.doi.org/10.1210/jcem.85.3.6402.

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Abstract How weight loss improves lipid levels is poorly understood. Cross-sectional studies have suggested that accumulation of fat in intraabdominal stores (IAF) may lead to abnormal lipid levels, increased hepatic lipase (HL) activity, and smaller low density lipoprotein (LDL) particle size. To determine what effect loss of IAF would have on lipid parameters, 21 healthy older men underwent diet-induced weight loss. During a period of weight stability before and after weight loss, subjects underwent studies of body composition, lipids, measurement of postheparin lipoprotein and HL lipase activities, cholesteryl ester transfer protein activity, and insulin sensitivity (Si). After an average weight loss of 10%, reductions in fat mass, IAF, and abdominal sc fat were seen, accompanied by reductions in levels of triglyceride, very low density lipoprotein cholesterol, apolipoprotein B, and HL activity. High density lipoprotein-2 cholesterol and Si increased. In those subjects with pattern B LDL at baseline, LDL particle size increased. Cholesteryl ester transfer protein activity did not change. Changes in IAF and Si correlated with a decrease in HL activity (although not independently of each other). In summary, in men undergoing diet-induced weight loss, only loss of IAF was found to be associated with a reduction in HL, which is associated with beneficial effects on lipid levels.

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Bovenschen, Niels, Koen Mertens, Lihui Hu, Louis M. Havekes, and Bart J. M. van Vlijmen. "LDL receptor cooperates with LDL receptor–related protein in regulating plasma levels of coagulation factor VIII in vivo." Blood 106, no. 3 (August 1, 2005): 906–12. http://dx.doi.org/10.1182/blood-2004-11-4230.

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Abstract Low-density lipoprotein (LDL) receptor (LDLR) and LDLR-related protein (LRP) are members of the LDLR family of endocytic receptors. LRP recognizes a wide spectrum of structurally and functionally unrelated ligands, including coagulation factor VIII (FVIII). In contrast, the ligand specificity of LDLR is restricted to apolipoproteins E and B-100. Ligand binding to the LDLR family is inhibited by receptor-associated protein (RAP). We have previously reported that, apart from LRP, other RAP-sensitive mechanisms contribute to the regulation of FVIII in vivo. In the present study, we showed that the extracellular ligand-binding domain of LDLR interacts with FVIII in vitro and that binding was inhibited by RAP. The physiologic relevance of the FVIII–LDLR interaction was addressed using mouse models of LDLR or hepatic LRP deficiency. In the absence of hepatic LRP, LDLR played a dominant role in the regulation and clearance of FVIII in vivo. Furthermore, FVIII clearance was accelerated after adenovirus-mediated gene transfer of LDLR. The role of LDLR in FVIII catabolism was not secondary to increased plasma lipoproteins or to changes in lipoprotein profiles. We propose that LDLR acts in concert with LRP in regulating plasma levels of FVIII in vivo. This represents a previously unrecognized link between LDLR and hemostasis.

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Watts, Gerald F., Juying Ji, Dick C. Chan, Esther M. M. Ooi, Anthony G. Johnson, Kerry-Anne Rye, and P. Hugh R. Barrett. "Relationships between changes in plasma lipid transfer proteins and apolipoprotein B-100 kinetics during fenofibrate treatment in the metabolic syndrome." Clinical Science 111, no. 3 (August 15, 2006): 193–99. http://dx.doi.org/10.1042/cs20060072.

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The aim of the present study was to investigate the association between changes in apoB (apolipoprotein B-100) kinetics and plasma PLTP (phospholipid transfer protein) and CETP (cholesteryl ester transfer protein) activities in men with MetS (the metabolic syndrome) treated with fenofibrate. Eleven men with MetS underwent a double-blind cross-over treatment with fenofibrate (200 mg/day) or placebo for 5 weeks. Compared with placebo, fenofibrate significantly increased the FCRs (fractional catabolic rates) of apoB in VLDL (very-low-density lipoprotein), IDL (intermediate-density lipoprotein) and LDL (low-density lipoprotein) (all P<0.01), with no significant reduction (−8%; P=0.131) in VLDL-apoB PR (production rate), but an almost significant increase (+15%, P=0.061) in LDL-apoB PR. Fenofibrate significantly lowered plasma TG [triacylglycerol (triglyceride); P<0.001], the VLDL-TG/apoB ratio (P=0.003) and CETP activity (P=0.004), but increased plasma HDL (high-density lipoprotein)-cholesterol concentration (P<0.001) and PLTP activity (P=0.03). The increase in PLTP activity was positively associated with the increase in both LDL-apoB FCR (r=0.641, P=0.034) and PR (r=0.625, P=0.040), and this was independent of the fall in plasma CETP activity and lathosterol level. The decrease in CETP activity was positively associated with the decrease in VLDL-apoB PR (r=0.615, P=0.044), but this association was not robust and not independent of changes in PLTP activity and lathosterol levels. Hence, in MetS, the effects of fenofibrate on plasma lipid transfer protein activities, especially PLTP activity, may partially explain the associated changes in apoB kinetics.

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Nelson, Adam J., Allan D. Sniderman, Marc Ditmarsch, Mary R. Dicklin, Stephen J. Nicholls, Michael H. Davidson, and John J. P. Kastelein. "Cholesteryl Ester Transfer Protein Inhibition Reduces Major Adverse Cardiovascular Events by Lowering Apolipoprotein B Levels." International Journal of Molecular Sciences 23, no. 16 (August 20, 2022): 9417. http://dx.doi.org/10.3390/ijms23169417.

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Cholesteryl ester transfer protein (CETP) facilitates the exchange of cholesteryl esters and triglycerides (TG) between high-density lipoprotein (HDL) particles and TG-rich, apolipoprotein (apo) B-containing particles. Initially, these compounds were developed to raise plasma HDL cholesterol (HDL-C) levels, a mechanism that was previously thought to lower the risk of atherosclerotic cardiovascular disease (ASCVD). More recently, the focus changed and the use of pharmacologic CETP inhibitors to reduce low-density lipoprotein cholesterol (LDL-C), non-HDL-C and apoB concentrations became supported by several lines of evidence from animal models, observational investigations, randomized controlled trials and Mendelian randomization studies. Furthermore, a cardiovascular outcome trial of anacetrapib demonstrated that CETP inhibition significantly reduced the risk of major coronary events in patients with ASCVD in a manner directly proportional to the substantial reduction in LDL-C and apoB. These data have dramatically shifted the attention on CETP away from raising HDL-C instead to lowering apoB-containing lipoproteins, which is relevant since the newest CETP inhibitor, obicetrapib, reduces LDL-C by up to 51% and apoB by up to 30% when taken in combination with a high-intensity statin. An ongoing cardiovascular outcome trial of obicetrapib in patients with ASCVD is expected to provide further evidence of the ability of CETP inhibitors to reduce major adverse cardiovascular events by lowering apoB. The purpose of the present review is to provide an up-to-date understanding of CETP inhibition and its relationship to ASCVD risk reduction.

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Hou, Jia-Rong, Yan-Hong Wang, Ying-Nan Zhong, Tong-Tong Che, Yang Hu, Jie Bao, and Ning Meng. "Protective Effect of Flavonoids from a Deep-Sea-Derived Arthrinium sp. against ox-LDL-Induced Oxidative Injury through Activating the AKT/Nrf2/HO-1 Pathway in Vascular Endothelial Cells." Marine Drugs 19, no. 12 (December 18, 2021): 712. http://dx.doi.org/10.3390/md19120712.

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Oxidized low-density lipoprotein (ox-LDL)-induced oxidative injury in vascular endothelial cells is crucial for the progression of cardiovascular diseases, including atherosclerosis. Several flavonoids have been shown cardiovascular protective effects. Recently, our research group confirmed that the novel flavonoids isolated from the deep-sea-derived fungus Arthrinium sp., 2,3,4,6,8-pentahydroxy-1-methylxanthone (compound 1) and arthone C (compound 2) effectively scavenged ROS in vitro. In this study, we further investigated whether these compounds could protect against ox-LDL-induced oxidative injury in endothelial cells and the underlying mechanisms. Our results showed that compounds 1 and 2 inhibited ox-LDL-induced apoptosis and adhesion factors expression in human umbilical vein vascular endothelial cells (HUVECs). Mechanistic studies showed that these compounds significantly inhibited the ROS level increase and the NF-κB nuclear translocation induced by ox-LDL. Moreover, compounds 1 and 2 activated the Nrf2 to transfer into nuclei and increased the expression of its downstream antioxidant gene HO-1 by inducing the phosphorylation of AKT in HUVECs. Importantly, the AKT inhibitor MK-2206 2HCl or knockdown of Nrf2 by RNA interference attenuated the inhibition effects of these compounds on ox-LDL-induced apoptosis in HUVECs. Meanwhile, knockdown of Nrf2 abolished the effects of the compounds on ox-LDL-induced ROS level increase and the translocation of NF-κB to nuclei. Collectively, the data showed that compounds 1 and 2 protected endothelial cells against ox-LDL-induced oxidative stress through activating the AKT/Nrf2/HO-1 pathway. Our study provides new strategies for the design of lead compounds for related cardiovascular diseases treatment.

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Kolovou, Genovefa, Marianna Stamatelatou, Katherine Anagnostopoulou, Peggy Kostakou, Vana Kolovou, Constantinos Mihas, Ioannis Vasiliadis, Olga Diakoumakou, Dimitri P. Mikhailidis, and Dennis V. Cokkinos. "Cholesteryl Ester Transfer Protein Gene Polymorphisms and Longevity Syndrome." Open Cardiovascular Medicine Journal 4, no. 1 (January 29, 2010): 14–19. http://dx.doi.org/10.2174/1874192401004010014.

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Purpose:High levels of high density lipoprotein (HDL) cholesterol are associated with a decreased risk of coronary heart disease (CHD). Subjects with high levels of HDL cholesterol (>70 mg/dl; 1.79 mmol/l) as well as high levels of low density lipoprotein (LDL) cholesterol, could represent a group with longevity syndrome (LS). Since HDL particles are influenced by cholesteryl ester transfer protein (CETP) activity, it is worth studying the CETP polymorphism. The aim of the study was to detect whether 2 genetic variants of the CETP are associated with the LS.Subjects and Methods:The study population consisted of 136 unrelated men and women with no personal and family history of CHD; 69 met the criteria for LS and 67 did not meet these criteria and had “normal” HDL cholesterol (>40 and <70 mg/dl; >1.03 and <1.79 mmol/l). All patients were genotyped for the TaqIB and I405V polymorphisms.Results:The B2 allele frequency of TaqIB polymorphism was higher in the LS in comparison with the non-LS group (p=0.03) whereas B1 allele frequency was higher in the non-LS group (p=0.03).Conclusions:Gene polymorphisms could help decide whether individuals who have increased levels of both LDL cholesterol and HDL cholesterol require treatment. Some of the prerequisites could include that subjects with LS should not only have very high levels of HDL cholesterol but also favorable gene polymorphisms. However, further investigations with a larger sample and including other gene polymorphisms, are needed.

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Li, Xiaochun, Piyali Saha, Jian Li, Günter Blobel, and Suzanne R. Pfeffer. "Clues to the mechanism of cholesterol transfer from the structure of NPC1 middle lumenal domain bound to NPC2." Proceedings of the National Academy of Sciences 113, no. 36 (August 22, 2016): 10079–84. http://dx.doi.org/10.1073/pnas.1611956113.

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Export of LDL-derived cholesterol from lysosomes requires the cooperation of the integral membrane protein Niemann–Pick C1 (NPC1) and a soluble protein, Niemann–Pick C2 (NPC2). Mutations in the genes encoding these proteins lead to Niemann–Pick disease type C (NPC). NPC2 binds to NPC1’s second (middle), lumenally oriented domain (MLD) and transfers cholesterol to NPC1’s N-terminal domain (NTD). Here, we report the 2.4-Å resolution crystal structure of a complex of human NPC1–MLD and NPC2 bearing bound cholesterol-3-O-sulfate. NPC1–MLD uses two protruding loops to bind NPC2, analogous to its interaction with the primed Ebola virus glycoprotein. Docking of the NPC1–NPC2 complex onto the full-length NPC1 structure reveals a direct cholesterol transfer tunnel between NPC2 and NTD cholesterol binding pockets, supporting the “hydrophobic hand-off” cholesterol transfer model.

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Leggiero, Eleonora, Giuseppe Labruna, Laura Iaffaldano, Barbara Lombardo, Adelaide Greco, Dario Fiorenza, Matteo Gramanzini, et al. "Helper-dependent adenovirus-mediated gene transfer of a secreted LDL receptor/transferrin chimeric protein reduces aortic atherosclerosis in LDL receptor-deficient mice." Gene Therapy 26, no. 3-4 (January 30, 2019): 121–30. http://dx.doi.org/10.1038/s41434-019-0061-z.

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Leggiero, Eleonora, Giuseppe Labruna, Laura Iaffaldano, Martina Esposito, Dalila Savoia, Lucia Sacchetti, and Lucio Pastore. "179. Helper-Dependent Adenovirus-Mediated Gene Transfer of an LDL Receptor/Transferrin Chimeric Protein Reduces Aortic Atherosclerosis in LDL Receptor-Deficient Mice." Molecular Therapy 24 (May 2016): S70. http://dx.doi.org/10.1016/s1525-0016(16)32988-4.

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Talmud, Philippa J., Karen L. Edwards, Clare M. Turner, Beth Newman, Jutta M. Palmen, Steve E. Humphries, and Melissa A. Austin. "Linkage of the Cholesteryl Ester Transfer Protein ( CETP ) Gene to LDL Particle Size." Circulation 101, no. 21 (May 30, 2000): 2461–66. http://dx.doi.org/10.1161/01.cir.101.21.2461.

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Li, Jianing, Sonja S. Pijut, Yuhuan Wang, Ailing Ji, Rupinder Kaur, Ryan E. Temel, Deneys R. van der Westhuyzen, and Gregory A. Graf. "Simultaneous Determination of Biliary and Intestinal Cholesterol Secretion Reveals That CETP (Cholesteryl Ester Transfer Protein) Alters Elimination Route in Mice." Arteriosclerosis, Thrombosis, and Vascular Biology 39, no. 10 (October 2019): 1986–95. http://dx.doi.org/10.1161/atvbaha.119.312952.

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Objective: Determine the impact of CETP (cholesteryl ester transfer protein) on the route of cholesterol elimination in mice. Approach and Results: We adapted our protocol for biliary cholesterol secretion with published methods for measuring transintestinal cholesterol elimination. Bile was diverted and biliary lipid secretion maintained by infusion of bile acid. The proximal small bowel was perfused with bile acid micelles. In high-fat, high-cholesterol–fed mice, the presence of a CETP transgene increased biliary cholesterol secretion at the expense of transintestinal cholesterol elimination. The increase in biliary cholesterol secretion was not associated with increases in hepatic SR-BI (scavenger receptor BI) or ABCG5 (ATP-binding cassette G5) ABCG8. The decline in intestinal cholesterol secretion was associated with an increase in intestinal Niemann-Pick disease, type C1, gene-like 1 mRNA. Finally, we followed the delivery of HDL (high-density lipoprotein) or LDL (low-density lipoprotein) cholesteryl esters (CE) from plasma to bile and intestinal perfusates. HDL-CE favored the biliary pathway. Following high-fat feeding, the presence of CETP directed HDL-CE away from the bile and towards the intestine. The presence of CETP increased LDL-CE delivery to bile, whereas the appearance of LDL-CE in intestinal perfusate was near the lower limit of detection. Conclusions: Biliary and intestinal cholesterol secretion can be simultaneously measured in mice and used as a model to examine factors that alter cholesterol elimination. Plasma factors, such as CETP, alter the route of cholesterol elimination from the body. Intestinal and biliary cholesterol secretion rates are independent of transhepatic or transintestinal delivery of HDL-CE, whereas LDL-CE was eliminated almost exclusively in the hepatobiliary pathway.

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Journal articles on the topic 'LDL transfer'

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