Plasma cholesteryl ester transfer protein is lowered by treatment of hypercholesterolemia with cholestyramine*

Carrilho, A.J.F.; Medina, Wilson L.; Nakandakare, Edna Regina; Quintão, Eder Carlos Rocha

doi:10.1016/s0009-9236(97)90154-5

Cited by 15 publications

(10 citation statements)

References 32 publications

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“…Interestingly, the simultaneous, although transient, decrease of LDL-C and of CETP concentrations elicited by hrGH supports other studies that have suggested a close relationship between LDL metabolism and the regulation of the CETP gene expression: (i) plasma CETP levels are high in primary hypercholesterolemic subjects (26,27), and diminish upon the administration of cholestyramine (29), a nonabsorbable drug that stimulates the gene expression of the hepatic LDL receptors; (ii) cholesterol feeding increases both the transcription of the human CETP gene (23) and the plasma CETP concentration (24) and diminishes the number of hepatic LDL receptors (25); (iii) these receptors are induced by GH treatment (30).…”

Section: Discussionsupporting

confidence: 81%

“…Evidence for an interrelationship between cholesterol metabolism and the regulation of plasma CETP levels is supported by the following observations: (i) in a variety of species, plasma CETP concentration and activity, as well as hepatic and peripheral CETP mRNA levels, increase in response to a highcholesterol diet (22)(23)(24) whereas the number of hepatic LDL receptors decreases (25); (ii) subjects with family-related hypercholesterolemia have high plasma CETP concentrations (26,27); (iii) simvastatin (28) and cholestyramine (29), wellknown hypocholesterolemic drugs, increase the expression of the hepatic LDL receptors and reduce the plasma CETP levels; and (iv) these receptors are induced by GH treatment (30). Tan et al (31) showed that plasma CETP activity is increased in acromegalic patients.…”

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confidence: 97%

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Plasma cholesteryl ester transfer protein and lipoprotein levels during treatment of growth hormone‐deficient adult humans

Carrilho

Cunha-Neto

Nunes

et al. 2001

Lipids

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The incidence of atherosclerosis is increased in growth hormone (GH) deficient-individuals. Nonetheless, the antiatherogenic benefits of GH replacement therapy remain uncertain. In this study the effect of human recombinant growth hormone (hrGH) replacement therapy administered to GH-deficient adults on the plasma cholesteryl ester transfer protein (CETP) concentration and activity was analyzed. These findings were related to changes in the concentrations of the plasma lipoproteins. The hrGH was administered for 12 mon to human GH-deficient patients (n = 13; 8 men, 5 women). During the study plasma lipoproteins were separated by ultracentrifugation, and plasma cholesterol esterification rate (CER), endogenous CETP activity, and CETP concentration were measured. GH replacement therapy transiently (at 3 mon) lowered plasma concentration of CETP and low density lipoprotein-cholesterol (LDL-C) and raised total triglycerides. Furthermore, hrGH permanently increased both the plasma lipoprotein(a) [Lp(a)] concentration, which is known as atherogenic, and the proportion of cholesteryl ester in the high density lipoprotein2 (HDL2) particles, which is potentially atheroprotective. The simultaneous decrease of the plasma CETP and LDL-C concentrations elicited by hrGH indicated a close relationship between LDL metabolism and the regulation of the CETP gene expression. Endogenous CETP activity and the CER were not modified because these parameters are regulated in opposite ways by plasma levels of triglycerides; that is, CER increased and CETP decreased.

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Section: Discussionsupporting

confidence: 81%

mentioning

confidence: 97%

Plasma cholesteryl ester transfer protein and lipoprotein levels during treatment of growth hormone‐deficient adult humans

Carrilho

Cunha-Neto

Nunes

et al. 2001

Lipids

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“…38,39 This may occur for 2 reasons: First, plasma CETP concentrations are increased. 19,23 Second, because the rates of net lipid transfer in plasma are strongly influenced by the concentration of VLDL TG, 14 CETP-mediated remodeling of VLDL composition is likely to be increased in these subjects and progressively enhanced as TG concentrations increase. Because VLDL and its remnants are more rapidly cleared from circulation than LDL, we hypothesize that the negative correlation of LTIP with plasma TG levels can be explained by the increased turnover of LTIP from the plasma compartment that is due to the redistribution of LTIP to particles with shorter plasma lifetimes.…”

Section: Discussionmentioning

confidence: 99%

“…Some (14 of 23) of these subjects are a subset of a previously reported group. 23 Additionally, 46 normolipidemic control subjects in good clinical health and without any known cardiovascular risk factors were studied. For reasons explained below, these controls are reported as 2 separate groups (control 1 and control 2, Table 1).…”

Section: Brazilian Subjectsmentioning

confidence: 99%

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Markedly Elevated Lipid Transfer Inhibitor Protein in Hypercholesterolemic Subjects Is Mitigated by Plasma Triglyceride Levels

Morton

Nunes

Izem

et al. 2001

ATVB

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Abstract-Lipid transfer inhibitor protein (LTIP, apolipoprotein F) regulates the interaction of cholesteryl ester transfer protein (CETP) with lipoproteins and is postulated to enhance the ability of CETP to stimulate reverse cholesterol transport. The factors that regulate LTIP levels and control its biosynthesis are unknown. Here, we demonstrate that plasma LTIP is dramatically increased (3-fold) in hypercholesterolemic subjects with normal to mildly elevated plasma triglyceride (TG) levels compared with control subjects. LTIP in these subjects is not correlated with the extent of hypercholesterolemia or with low density lipoprotein (LDL), high density lipoprotein, or CETP levels. [3][4][5] However, the overall impact of CETP activity on atherogenesis has remained controversial, inasmuch as CETP can potentially facilitate processes that would appear to be proatherogenic and antiatherogenic.CETP activity is regulated by another plasma component, lipid transfer inhibitor protein (LTIP). We recently purified and cloned LTIP and demonstrated its identity with apoF. 6 Although LTIP was first identified simply by its capacity to suppress CETP activity in binary lipid transfer assays, 7 it now appears that LTIP plays a more complex role in regulating CETP. CETP has little preference for interacting with different lipoprotein classes under steady-state conditions, 8 and within a mixture of lipoproteins, CETP mediates transfer events between lipoprotein classes at rates that are largely determined by their relative concentrations. 9 This finding contrasts with that seen in plasma, in which HDL appears to be a preferred CETP substrate. 10 -12 We have recently demonstrated that LTIP activity accounts for this discrepancy. 9 This is hypothesized to occur because LTIP preferentially suppresses the interaction of CETP with LDL. 13 Because VLDL concentrations are rate limiting in normal plasma to the CE-TG exchange process, 14 the suppression of transfers with LDL results in a stimulation of lipid exchange between VLDL and HDL. 9,15 Therefore, LTIP is a regulator of CETP function in that it controls the rate of individual lipid transfer reactions. We have proposed that LTIP augments the antiatherogenic capacities of CETP by stimulating reverse cholesterol transport. 9,15 CETP synthesis is strongly upregulated by cholesterol, 16,17 and elevated CETP levels are commonly observed in hypercholesterolemic subjects. 18,19 This appears to be an adaptive response to enhance mechanisms responsible for sterol homeostasis. Because the beneficial actions of CETP are likely to be enhanced by LTIP, it seems reasonable that LTIP levels may be increased by similar stimuli. At present, nothing is

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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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Plasma cholesteryl ester transfer protein is lowered by treatment of hypercholesterolemia with cholestyramine*

Cited by 15 publications

References 32 publications

Plasma cholesteryl ester transfer protein and lipoprotein levels during treatment of growth hormone‐deficient adult humans

Plasma cholesteryl ester transfer protein and lipoprotein levels during treatment of growth hormone‐deficient adult humans

Markedly Elevated Lipid Transfer Inhibitor Protein in Hypercholesterolemic Subjects Is Mitigated by Plasma Triglyceride Levels

Reverse cholesterol transport in diabetes mellitus

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