Ester Transfer Research Articles

Abstract P112: A Simple, Rapid, And Sensitive Fluorescence-based Method To Assess Triacylglycerol Hydrolase Activities

Introduction: Lipases constitute an important class of water-soluble enzymes that catalyze the hydrolysis of hydrophobic triacylglycerol (TAG). Their activity is usually measured after isolation and quantification of the hydrolyzed free fatty acids. We have used NBD-labeled lipids previously to develop TAG, cholesteryl ester, and phospholipid transfer assays for microsomal triglyceride transfer protein. To date, however, NBD-labeled TAG (NBD-TAG) has not been used to assess the enzymatic activities of different lipases. Methods: We developed methods to measure lipase activities using adipose triglyceride lipase (ATGL), lipoprotein lipase (LpL), and pancreatic triglyceride lipase (PNLIP) as model lipases. In these assays, we incubated a source of ATGL, LpL, or PNLIP with substrate emulsions containing nitrobenzoxadiazole (NBD)-labeled TAG in phosphatidylcholine (PC) and phosphatidylinositol (PI), measured increases in NBD fluorescence with time, and calculated enzyme activities. Results: Incorporation of NBD-TAG into PC vesicles resulted in some hydrolysis; but required product isolation step to measure NBD fluorescence. However, incorporation of PI into these NBD-TAG/PC vesicles significantly increased substrate hydrolysis in time, protein, and substrate concentration dependent manner negating the need to isolate products to measure lipase activities. Further, increasing the ratio of NBD-TAG to PC enhanced substrate hydrolysis. Next, we tested specific lipase inhibitors and found that orlistat inhibits all three enzymes indicating that it is a pan-lipase inhibitor. Conclusions: We describe a simple, rapid fluorescence-based TAG hydrolysis assay to assess three major TAG hydrolases: ATGL localized intracellularly, LpL localized at the extracellular endothelium, and PNLIP produced and secreted from the pancreas into the intestinal lumen. The major advantages of this method are its speed, simplicity, and avoidance of a product isolation step. This assay is potentially applicable to a wide range of lipases and is amenable to high-throughput screening to discover novel modulators of triacylglycerol hydrolases, and in the diagnosis of diseases associated with increases in plasma lipase activities.

CETP Gene and Its Role in Diabetes Mellitus Type II - A Review

Plasma lipoproteins are continuously remodelled through the actions of enzymes and lipid transfer proteins. In particular, the transfers of cholesteryl esters (CE) and triglycerides (TG) are facilitated by a specialized protein known as the cholesteryl ester transfer protein (CETP). Genetic polymorphisms of the enzymes and proteins involved in lipid metabolism like cholesteryl ester transfer protein CETP have been shown to affect plasma lipid concentrations. CETP modifies HDL, LDL and very low density lipoprotein (VLDL) levels. It transfers cholesterol esters (CE) from CE rich particles (HDL and LDL) to triglyceride rich particles (VLDL) in exchange of triglyceride from the latter. Several genetic polymorphisms have been reported which may be associated with alteration in CETP activity. TaqI B polymorphism has been most widely studied, which results from a silent mutation in nucleotide 277, in intron 1 of the gene. The polymorphism has been associated with decreased CETP mass and an increase in HDL-cholesterol. The TaqI polymorphism B1 allele of CETP has been shown to be an independent risk factor for development of cerebral vascular disease, in patients with T2DM.

HPS2-THRIVE, AIM-HIGH and dal-OUTCOMES: HDL-cholesterol under attack.

A low level of high-density lipoprotein cholesterol (HDL-C) is an established predictor of the risk of coronary heart disease (CHD).1 HDL promotes cellular cholesterol efflux and reverse cholesterol transport from lipid-laden macrophages (Figure 1), and prevents lipoprotein oxidation. A linear inverse relation has been reported in many observational studies between plasma HDL-C level and incident CHD events, with a plateau effect at HDL-C values >90 mg/dL in men and 75 mg/dL in women.2 However, it remains uncertain whether raising HDL-C levels therapeutically (by either niacin or cholesterol ester transfer protein “CETP” inhibitors) would reduce subsequent cardiovascular (CV) events beyond that achieved with intensive statin therapy. Figure 1. Reverse Cholesterol Transport. ABCA1, ATP binding cassette A1 transporter; ABCG1, ATP binding cassette G1 transporter; CETP, cholesterol ester transfer protein; SR-B1: Scavenger receptor-B1; LDLR, low density lipoprotein receptor. Niacin has multiple beneficial effects on serum lipoproteins;3 (1) it raises HDL-C level primarily by promoting the production and retarding the catabolism of Apo A1 in the liver, and also by stimulating ATP-binding cassette transporter A1 which augments reverse cholesterol transport. (2) It decreases the secretion of very low density lipoprotein (VLDL) particles from the liver with subsequent reduction of both intermediate density lipoprotein (IDL) and low density lipoprotein (LDL) particles; an effect mediated by inhibition of hormone-sensitive lipase in the adipose tissue, and hepatocyte diacylglycerol acyltransferase-2 (DGAT-2). (3) It is unique in lowering lipoprotein (a) levels by up to 30%. (4) It inhibits oxidative stress, key inflammatory genes, cytokines involved in atherosclerosis. Inhibition of CETP by torcetrapib, dalcetrapib, anacetrapib, and evacetrapib is another attractive strategy to raise plasma HDL-C level.4,5 CETP promotes the transfer of cholesterol esters from HDL to triglyceride-rich lipoprotein particles, in exchange for triglyceride, thereby reducing the circulating HDL-C concentration. Over the past years, numerous randomized clinical studies have been conducted to assess the clinical efficacy and safety of these drugs.

Anacetrapib

Anacetrapib is a cholesteryl ester transfer protein (CETP) inhibitor currently in Phase III of development as a treatment for those with dyslipidemia and the risk of cardiovascular disease. The agent acts by inhibiting the CETP, which mediates the transfer of cholesterol esters from high-density lipoprotein cholesterol (HDL-C) to other lipoproteins. HDL-C has been inversely linked to cardiac risk and is thus a potential target for decreasing residual cardiovascular risk, which remains despite aggressive low-density lipoprotein cholesterol therapy with statin drugs. Anacetrapib has been shown to raise HDL-C by up to 138% and decrease low-density lipoprotein cholesterol by up to 39% compared with placebo. The HDL-C molecules treated with anacetrapib have also been shown to retain their function in cholesterol efflux and reverse cholesterol transport and their anti-inflammatory properties. Unlike the previously tested CETP inhibitor torcetrapib, anacetrapib has not been shown to elevate blood pressure, alter electrolytes, or cause any significant side effects. Future studies will determine whether these alterations in the lipid profile decrease the cardiovascular risk of morbidity and mortality. If these studies show promising results, anacetrapib could become a vital pharmacologic therapy for decreasing cardiovascular risk in patients.

CETP TaqIB Polymorphism, Serum Lipid Levels And Risk Of Atrial Fibrillation: A Case-Control Study.

The cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl esters from high-density lipoproteins (HDL) to triglyceride (TG)-rich lipoproteins. A consistent number of investigations has suggested an association between the TaqIB polymorphism of the CETP gene, plasma HDL-C levels and the risk of cardiovascular disease, but the results are controversial. The aim of this study was to determine if the TaqIB polymorphism might be related to the presence of atrial fibrillation (AF). We conducted a case-control study, enrolling 109 Caucasian unrelated patients coming from Salento (Southern Italy) with documented AF and 109 controls selected from the same ward. The CETP TaqIB genotypes were determined by RFLP-PCR. The subjects with the B2B2 genotype seem to be more susceptible to AF development (OR=2.28, 95% CI 1.06-4.89, p=0.032). The AF incidence is higher if we consider only the female subgroup (OR=5.14, 95% CI 1.57-16.82, p=0.0061). In the AF female subgroup the B2B2 patients had a statistically significant decrease of HDL-C levels (1.50 ± 0.35 vs 2.07 ± 0.42; p=0.012) and statistically higher TG levels (1.34 ± 0.46 vs 0.77 ± 0.14; p=0.027) and TG/HDL-C ratio (2.14 ± 0.80 vs 0.88 ± 0.23; p=0.007) when compared to B2B2 female control subjects. When we analyzed the linkage between the TaqIB polymorphism and the promoter variant (-629C/A), we found that 100% of the B2 alleles of the TaqIB polymorphism were associated with the A alleles of the -629 promoter polymorphism in our subjects. This study suggests that in post-menopausal women atrial fibrillation could be promoted by the association of CETP B2B2/AA genotype with higher triglycerides values.

Abstract 411: Vasculoprotective Function of HDL from Cetp-deficient Subjects

Objective- Cholesteryl ester transfer protein (CETP) is a plasma glycoprotein that catalyses the transfer of cholesteryl esters from HDL to the other plasma lipoproteins. Genetic deficiency of CETP is one of the known causes of primary hyperalphalipoproteinemia and represents a unique tool to evaluate how structural HDL alterations impact on HDL atheroprotective activity. Aim of the present study was to assess the vasculoprotective activity of HDL isolated from carriers of genetic CETP deficiency. Subjects and Methods- HDL and HDL subfractions were isolated from carriers of the R37X, Q165X and IVS7+1 CETP mutations and tested for their protein/lipid composition and their anti-inflammatory and NO-promoting activity in endothelial cells. Results- HDL and HDL3 from carriers proved to be as effective as control HDL in down-regulating cytokine-induced VCAM-1 expression and in enhancing eNOS expression in endothelial cells. Interestingly, carriers’ HDL2 were significantly more efficient than HDL2 from controls in inhibiting VCAM-1 and enhancing eNOS expression, likely due to their peculiar lipid composition and their higher content of apoE. On the contrary, carriers’ HDL and HDL subfractions were less effective than lipoproteins from controls in stimulating eNOS activation by phosphorylation and NO production, likely because of a reduced content of S1P in carriers’ HDL. Conclusions- Large, apoE-enriched HDL that accumulate in genetic CETP deficiency retain their ability to preserve endothelial cell homeostasis, supporting the use of pharmacological CETP inhibition to increase HDL levels and enhance HDL-mediated atheroprotection.

The inhibition of cholesteryl ester transfer protein: a long and winding road

The presence in human plasma of a protein that promotes bidirectional transfers of neutral lipids (cholesteryl esters and triglycerides) between all lipoprotein particles was first reported in 1978 (1, 2). This protein was identified as cholesteryl ester transfer protein (CETP) and subsequently cloned in 1987 by Drayna et al. (3). CETP promotes the equilibration of cholesteryl esters and triglycerides between HDL, LDL, and triglyceride-rich lipoproteins (TRL), which include VLDL that are produced in the liver, intestinally-derived chylomicrons, and chylomicron remnants. As most of the cholesteryl esters in plasma originate in HDL in the reaction catalyzed by lecithin:cholesterol acyltransferase, and triglycerides mostly enter the plasma compartment as a component of TRL, this process of equilibration results in a net mass transfer of cholesteryl esters from potentially anti-atherogenic HDL particles to LDL and TRL, which are known to be atherogenic.

Thermochemistry of ethyl acetate solvation in the 1-octanol-N,N-dimethylformamide system

The thermal effects of ethyl acetate (EtOAc), 1-octanol (OctOH), and N,N-dimethylformamide (DMF) solution in a OctOH-DMF model system were measured using a calorimeter of variable temperature with an isothermal shell at 298 K. The standard enthalpies of solution and ester transfer from an alcohol to a binary mixture, and partial mole enthalpies of mixed solvent components were determined. The state of non-electrolyte molecules in OctOH-DMF and OctOH-DMF-EtOAc systems were studied using extended coordination model. It was found that the binary solvent is subjected to microclusterization, since the fraction of the single-type molecules in the solvation sphere of both components of a mixture is significantly higher than in the liquid phase volume. The conclusion was drawn that in the triple system, the ethyl acetate solvation sphere in the whole range of compositions is significantly enriched with amide owing to stronger esteramide dipole-dipole interaction.

Is there a future for CETP-inhibitor therapy?

Despite large improvements in cardiovascular disease mortality, coronary heart disease (CHD) and stroke remain the leading causes of death in most nations around the world [1,101]. Statins are the foundation for cardiovascular prevention, with up to 50% reductions in cardiovascular risk with the more potent statins [2]. In both statin-treated and -untreated patients, low levels of high-density lipoprotein cholesterol (HDL-C) are an important predictor of subsequent cardiovascular risk [3,4]. In epidemiologic studies, each 1 mg/dl (0.03 mmol, or ~2–3%, depending on baseline HDL-C level) increase in HDL-C is associated with a 2–4% reduction in the risk of CHD events, independent of low-density lipoprotein cholesterol (LDL-C) levels [5]. Of the drugs currently on the market, niacin is the most effective at raising HDL-C (~25% at the 2-g dose), while statins and fibrates have more modest HDL-C-raising effects (3–10%) [6]. However, it is not clear that pharmacologically raising HDL-C per se with these agents reduces cardiovascular risk. A meta-ana lysis of HDL-C-raising drugs found that after adjusting for LDL-C-lowering, raising HDL-C (or lowering triglycerides) was not associated with further cardiovascular risk reduction [6]. Several classes of HDL-C-raising agents with novel mechanisms of action are under development [7]. Farthest along are the cholesteryl ester transfer protein (CETP) inhibitors. CETP mediates the transfer of cholesteryl esters from HDL to proatherogenic apolipoprotein B-lipoproteins for transportation of cholesterol back to the cells; blocking CETP increases levels of mature HDL-C particles. The first CETP inhibitor to move into clinical trials was torcetrapib (Pfizer, Inc). Despite large increases in HDL-C, development of torcetrapib was terminated due to excess mortality in the torcetrapib group of the large outcomes trial, Investigation of Lipid Level management to Understand its Impact in Atherosclerotic Events (ILLUMINATE). Increased mortality in the torcetrapib-treated group occurred despite a 72% increase in HDL-C and a 25% decrease in LDL-C [8]. Torcetrapib also had no benefit on atherosclerotic progression in two noninvasive imaging studies, despite similar lipid changes [9,10]. The adverse mortality effect of torcetrapib has been largely attributed to accelerated hypertension due to activation of the renin–angiotensin–aldosterone system through a non-CETP-dependent effect [11]. Other mechanisms, such as lack of HDL functionality and proinflammatory effects, have also been proposed to explain torcetrapib’s adverse effects. Two CETP inhibitors are still in development, anacetrapib and dalcetrapib. Neither agent has been found to increase blood pressure or influence the renin– angiotensin–aldosterone axis in studies to date [7]. The more potent CETP inhibitor, anacetrapib, comes from the same chemical class as torcetrapib and strongly binds to the CETP molecule. Added to optimal statin therapy, anacetrapib 100 mg has been shown to increase HDL-C by 138% and reduce LDL-C an additional 40%, with modest triglyceride-lowering effects [12]. The less potent dalcetrapib is from a different chemical class, binds reversibly to and induces a different conformational “Given the excess mortality caused by torcetrapib, it is unlikely that any CETP inhibitor will receive regulatory approval prior to the completion of the long-term cardiovascular end point trials...”

CETP TaqIB polymorphisms and CETP activity in normolipidemic healthy northern Indians

Summary Background and aim Asian Indians have relatively lower high-density lipoprotein cholesterol (HDL-C) as compared to the other populations. Cholesterol ester transfer protein (CETP) is involved in the transfer of cholesterol esters from HDL-C to other lipoproteins in the plasma. In order to assess the role of CETP polymorphisms and their association with HDL-C, if any, we have studied the TaqIB polymorphism in intron 1 of CETP and its correlation with plasma lipids in 158 normolipidemic healthy subjects. Methods and results Plasma lipids levels were estimated using commercially available kits from Randox (India) and CETP TaqIB polymorphism were assayed by PCR-RFLP in 158 healthy normolipidemic individuals. The observed allelic frequencies of TaqIB polymorphisms, B1 and B2 were 43.0% and 56.9%, respectively. Lipid parameters were comparable between individuals with the different CETP TaqIB polymorphisms. The individuals categorized on the basis of their HDL-C levels ( 1.04 mmol/l), had comparable distribution of CETP genotypes. CETP activity was assessed in 84 of the total 158 individuals included in the study and did not vary among the CETP TaqIB genotypes. CETP activity in the females ( n = 39) negatively correlated with HDL-C levels. Conclusion This study reveals that CETP TaqIB polymorphisms are not associated with the decreased levels of HDL-C in healthy normolipidemic individuals. We are presently involved in studies to assess the precise role of CETP TaqIB polymorphism and CETP activity in hyperlipidemia in Asian Indians.

CETP-Inhibitoren (Torcetrapib und JTT-705)

Although results from clinical outcome studies and from studies on atherosclerosis progression have convincingly demonstrated that LDL-cholesterol lowering by statins may significantly reduce the incidence of cardiovascular events, these studies have also indicated that LDL lowering alone with standard statin doses leaves a considerable residual cardiovascular risk. Apart from LDL, HDL has been recognized as an important independent risk factor for coronary heart disease and HDL raising has been associated with coronary heart disease reduction, probably by its anti-atheroclerotic properties (HDL-mediated reverse cholesterol transport, anti-inflammatory and anti oxidant properties). Therapies to raise HDL are therefore of major scientific importance. The most important increase in HDL-cholesterol is presently achieved by inhibition of the cholesterol ester transport protein (CETP), a protein which mediates the transfer of cholesterol esters from HDL to VLDL/LDL and of trigylcerides from VLDL/IDL to HDL. At the present time two inhibitors of CETP are under clinical investigation, Torcetrapib and JTT705. These drugs increase HDL cholesterol by 30 to 100%. They moderately lower VLDL/LDL-cholesterol and they normalize small dense LDL. Raising HDL by CETP inhibition in combination with a statin could prove to be en efficient new approach against atherosclerosis.

New Approach to Raising HDL Levels

Inhibition of cholesteryl ester transfer protein (CETP), a plasma glycoprotein that aids in the transfer of cholesterol esters from HDL cholesterol to

Plasma cholesteryl ester transfer protein activity in hyper- and hypothyroidism.

Thyroid dysfunction is associated with multiple changes in lipoprotein metabolism, and we have determined the effects of thyroid dysfunction on plasma cholesteryl ester transfer protein (CETP) activity. CETP is a plasma protein that mediates the exchange of cholesteryl ester and triglyceride between plasma lipoproteins and plays an important role in high-density lipoprotein metabolism and in the reverse cholesterol transport pathway. Plasma CETP activity was assayed in 18 hyperthyroid and in 17 hypothyroid patients, before and after treatment, by measuring the transfer of cholesteryl esters from exogenous radiolabeled high-density lipoprotein to apolipoprotein B-containing lipoproteins. Plasma CETP activity was increased in hyperthyroid patients, compared with their matched controls (22.11 +/- 8.92% transferred/5 microL.4 h vs. 16.75 +/- 6.48, P < 0.05), whereas in hypothyroid patients, plasma CETP activity was decreased (11.14 +/- 4.84% transferred/5 microL.4 h vs. 17.26 +/- 7.13, P < 0.01). Plasma CETP activity decreased after treatment of thyrotoxicosis, although a significant change was observed, mainly in the severely thyrotoxic patients with free T4 > 100 pmol/L (n = 11, 25.61 +/- 8.12% transferred/5 microL.4 h vs. 21.71 +/- 7.84, P < 0.05). In the hypothyroid patients, there was a significant increase in plasma CETP activity after thyroxine replacement (11.14 +/- 4.84% transferred/5 microL.4 h vs. 15.46 +/- 6.71, P < 0.01). There was a strong positive correlation between log(free T4) and plasma CETP activity (r = 0.51, P < 0.001). In summary, both hyper- and hypothyroidism are associated with significant changes in plasma CETP activity, and these changes are corrected when the patients have been rendered euthyroid.

Transfer of dehydroepiandrosterone- and pregnenolone-fatty acid esters between human lipoproteins.

Dehydroepiandrosterone (DHEA)- and pregnenolone (PREG)-fatty acid esters (FA) are formed in plasma high density lipoproteins (HDL), whereas they accumulate in very low density lipoproteins (VLDL), low density lipoproteins (LDL), and HDL. We have hypothesized that these lipoidal steroids could be transferred from HDL to VLDL and LDL by the cholesteryl ester (CE) transfer protein (CETP), which mediates CE transfer activity in human plasma. In this study, we further investigated this hypothesis. Lipoproteins and lipoprotein-deficient plasma (LPDP) were purified and analyzed by Western blots. LPDP was rich in CETP, in contrast to lipoprotein preparations, which contained very low amounts. Using these preparations in in vitro transfer assays, CE transfer from radiolabeled steroid ester-HDL to VLDL or LDL was only observed in the presence of LPDP. In contrast, time- and temperature-dependent transfer of DHEA-FA and PREG-FA were observed in the absence of LPDP. The addition of LPDP had no effect on the DHEA-FA transfer rate, whereas the PREG-FA transfer rate was increased. Moreover, in the absence of LPDP, no decrease in the transfer levels of DHEA-FA and PREG-FA was observed after the removal of CETP from lipoprotein preparations by immunoaffinity column chromatography. The PREG-FA transfer activity of LPDP was studied using the anti-CETP monoclonal antibody TP-2, which is known to block the CE transfer activity of CETP. In the presence of LPDP, this antibody led to a dose-dependent decrease in CE transfer activity, whereas PREG-FA transfer activity was unaffected. In conclusion, we have shown that DHEA-FA and PREG-FA are transferred from HDL to VLDL and LDL by a CETP-independent mechanism. There is a major difference in the transport of lipoidal steroids by human lipoproteins compared to that of CE.

Cholesteryl ester transfer protein: an enigmatic protein.

The cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl esters from high-density lipoproteins (HDL) into very-low-density lipoproteins (VLDL) with a reciprocal exchange of triglycerides. Plasma CETP is mainly bound to HDL and is involved in the interconversion of these lipoproteins. In experimental models such as transgenic mice, CETP activity decreases HDL cholesterol and increases the cholesteryl ester content of apo B-containing lipoproteins. In humans, CETP activity and concentration are positively correlated with VLDL-LDL cholesterol. Clinical studies suggest that the effect of CETP on HDL cholesterol depends on the amount of acceptor lipoproteins. CETP activity is negatively correlated with HDL cholesterol only in hypertriglyceridemic states. Various CETP gene mutations have been reported, they induce hyper-alpha-lipoproteinemia. On the other hand, the impact of the variability of CETP gene on HDL cholesterol variations in Caucasians is controversial. CETP is often involved in secondary dyslipidemia and is susceptible to modify the composition of plasma lipoproteins in an atherogenic way. The real impact of CETP activity on atherosclerosis is still unknown. CETP is susceptible to play a proatherogenic role since it mediates a redistribution of plasma cholesterol from lipoproteins associated with a protection against atherosclerosis into the proatherogenic apo B-containing lipoproteins. However, CETP mediates one of the steps of the reverse cholesterol transport, an antiatherogenic process that channels cholesterol from peripheral tissues back to the liver.

Increased net mass transfer of cholesteryl esters and phospholipid transfer protein activity but normal cholesteryl ester transfer protein mass and activity in patients with peripheral vascular disease

Increased net mass transfer of cholesteryl esters and phospholipid transfer protein activity but normal cholesteryl ester transfer protein mass and activity in patients with peripheral vascular disease

Co-expression of cholesteryl ester transfer protein and defective apolipoprotein E in transgenic mice alters plasma cholesterol distribution. Implications for the pathogenesis of type III hyperlipoproteinemia.

Despite the definite etiologic link between apolipoprotein (apo) E mutations and type III hyperlipoproteinemia (HLP), it is not clear what additional factors are involved in the development of florid hyperlipidemia and how to explain the wide variability in the expression of the hyperlipidemic phenotype in carriers of receptor binding-defective apoE variants. The present study was designed to determine whether the overexpression of cholesteryl ester transfer protein (CETP), a plasma protein that transfers cholesteryl esters from the high density lipoproteins (HDL) to the very low density lipoproteins (VLDL) and whose activity is increased in hyperlipidemic states, plays a role in the development of hyperlipidemia and beta-VLDL accumulation in type III HLP. We produced double-transgenic mice that co-expressed high levels of simian CETP and either high or low levels of a human receptor binding-defective apoE variant, apoE(Cys-142). We previously reported that apoE(Cys-142) high-expresser mice showed spontaneous hyperlipidemia and accumulation of beta-VLDL, whereas the low-expresser mice showed only a modest increase in VLDL cholesterol. Co-expression of CETP induced a massive transfer of cholesteryl esters from the HDL to the VLDL in both lines of double-transgenic mice. As a result, HDL cholesterol and apoA-I levels were reduced to about 50% of normal, VLDL cholesterol increased 2.5-fold, and the cholesteryl ester content of VLDL reached values similar to those observed in human beta-VLDL. The ratio of defective to normal apoE in VLDL was unaffected by CETP co-expression and was higher in animals expressing high apoE levels. Finally, in spite of an increased accumulation of beta-VLDL in the high-expresser mice, the VLDL of the low-expresser mice maintained pre-beta mobility upon co-expression of CETP. The results of this study demonstrate that the ratio of defective to normal apoE on the VLDL, rather than the cholesteryl ester content of VLDL, is the major factor determining the development of severe hyperlipidemia and the formation and accumulation of beta-VLDL in type III HLP.

Effect of pravastatin on the transfer of cholesteryl esters from HDL to VLDL and LDL (CET) in the fasting and postprandial state in patients with type 2 diabetes mellitus (DM)

Effect of pravastatin on the transfer of cholesteryl esters from HDL to VLDL and LDL (CET) in the fasting and postprandial state in patients with type 2 diabetes mellitus (DM)

Transfer of cholesteryl esters from HDL to VLDL and LDL (CET) is increased in patients with type 2 diabetes mellitus (DM)

Transfer of cholesteryl esters from HDL to VLDL and LDL (CET) is increased in patients with type 2 diabetes mellitus (DM)

Movement of core lipids among the plasma lipoproteins during cholesteryl ester (CE) transfer (CET) is not a molar exchange

Movement of core lipids among the plasma lipoproteins during cholesteryl ester (CE) transfer (CET) is not a molar exchange