CETP Concentration Research Articles

Cholesteryl Ester Transfer Protein Inhibitory Activity of New 4-Bromophenethyl Benzamides

Cardiovascular diseases, as coronary heart disease, heart failure, and hypertension are the first leading cause of death in the United States and the third globally. CETP is a glycoprotein excreted mainly from the liver and found in plasma. Normal plasma CETP concentration is 1-4 µg/ml, while the ratio increased 70-80% in dyslipidemic patients. There is a growing need for new CETP inhibitors which encourages us to conduct this research. In this work, synthesis and in vitro study for four new 4-bromophenethylbenzamides 9a-d were carried out. In vitro study showed that the targeted compounds 9a-d exhibit acceptable activity against CETP, where compound 9a has a % inhibition of 40.7 at 10 µM concentration. It was found that the presence of the oxy group in both 9a and 9c enhances their activity which could be attributed to Hydrogen-bond formation with the amino acid residues of the CETP binding site.

Study of effect modifiers of genetically predicted CETP reduction.

Genetic variants in drug targets can be used to predict the long-term, on-target effect of drugs. Here, we extend this principle to assess how sex and body mass index may modify the effect of genetically predicted lower CETP levelson biomarkers and cardiovascular outcomes. We found sex and body mass index(BMI) to be modifiers of the association between genetically predicted lower CETP and lipid biomarkers in UK Biobank participants. Female sex and lower BMI were associated with higher high-density lipoprotein cholesterol and lower low-density lipoprotein cholesterol for the same genetically predicted reduction in CETP concentration. We found that sex also modulated the effect of genetically lower CETP on cholesterol efflux capacity in samples from the Montreal Heart Institute Biobank. However, these modifying effects did not extend to sex differences in cardiovascular outcomes in our data. Our results provide insight into the clinical effects of CETP inhibitors in the presence of effect modification based on genetic data. The approach can support precision medicine applications and help assess the external validity of clinical trials.

Joint Genetic Inhibition of PCSK9 and CETP and the Association With Coronary Artery Disease

Cholesteryl ester transfer protein inhibition (CETP) has been shown to increase levels of high-density lipoprotein cholesterol (HDL-C) and reduce levels of low-density lipoprotein cholesterol (LDL-C). Current LDL-C target attainment is low, and novel phase 3 trials are underway to investigate whether CETP inhibitors result in reduction of cardiovascular disease risk in high-risk patients who may be treated with PCSK9-inhibiting agents. To explore the associations of combined reduction of CETP and PCSK9 concentrations with risk of coronary artery disease (CAD) and other clinical and safety outcomes. Two-sample 2 × 2 factorial Mendelian randomization study in a general population sample that includes data for UK Biobank participants of European ancestry. Separate genetic scores were constructed for CETP and PCSK9 plasma protein concentrations, which were combined to determine the associations of combined genetically reduced CETP and PCSK9 concentrations with disease. Blood lipid and lipoprotein concentrations, blood pressure, CAD, age-related macular degeneration, type 2 diabetes, any stroke and ischemic stroke, Alzheimer disease, vascular dementia, heart failure, atrial fibrillation, chronic kidney disease, asthma, and multiple sclerosis. Data for 425 354 UKB participants were included; the median (IQR) age was 59 years (51-64), and 229 399 (53.9%) were female. The associations of lower CETP and lower PCSK9 concentrations with CAD are similar when scaled per 10-mg/dL reduction in LDL-C concentrations (CETP: odds ratio [OR], 0.74; 95% CI, 0.67 to 0.81; PCSK9: OR, 0.75; 95% CI, 0.71 to 0.79). Combined exposure to lower CETP and PCSK9 concentrations was associated with an additive magnitude with lipids and all outcomes, and we did not observe any nonadditive interactions, most notably for LDL-C (CETP: effect size, -1.11 mg/dL; 95% CI, -1.40 to -0.82; PCSK9: effect size, -2.13 mg/dL; 95% CI, -2.43 to -1.84; combined: effect size, -3.47 mg/dL; 95% CI, -3.76 to -3.18; P = .34 for interaction) and CAD (CETP: OR, 0.96; 95% CI, 0.94 to 1.00; PCSK9: OR, 0.94; 95% CI, 0.91 to 0.97; combined: OR, 0.90; 95% CI, 0.87 to 0.93; P = .83 for interaction). In addition, when corrected for multiple testing, lower CETP concentrations were associated with increased age-related macular degeneration (OR, 1.11; 95% CI, 1.04 to 1.19). Our results suggest that joint inhibition of CETP and PCSK9 has additive effects on lipid traits and disease risk, including a lower risk of CAD. Further research may explore whether a combination of CETP- and PCSK9-related therapeutics can benefit high-risk patients who are unable to reach treatment targets with existing options.

Suppression of serum lipid transfer proteins involved in high-density lipoprotein cholesterol metabolism by intensive insulin therapy in the first year of type 1 diabetes mellitus: Prospective InLipoDiab1 study

Background and aimsCholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) are crucial proteins in reverse cholesterol transport. There are insufficient data on regulating these proteins by insulin therapy in type 1 diabetes mellitus (T1DM). We aimed to assess prospectively the impact of insulin therapy initiation on transfer proteins serum levels in adults with newly diagnosed T1DM. Methods and results57 adults with newly diagnosed T1DM were enrolled in the InLipoDiab1 Study. All participants were treated with subcutaneous insulin in the model of intensive insulin therapy since the diagnosis of diabetes. Serum PLTP and CETP concentrations were measured at diagnosis, after three weeks, six months, and after one year of insulin treatment, using the immunoenzymatic method ELISA.A significant decrease in PLTP and CETP concentrations were demonstrated during twelve months of insulin therapy in newly diagnosed T1DM. The dynamics of changes in the level of these proteins varied depending on the occurrence of remission after a year of the disease. In the group without remission, a significant decrease in PLTP and CETP levels appeared after six months of follow-up. The remission group was characterized by a decrease in proteins concentration only after one year of treatment. In the non-remission group, significant negative correlations were found between the daily dose of insulin and levels of PLTP and CETP. ConclusionExogenous insulin is an inhibitor of lipid transfer proteins involved in high-density lipoprotein cholesterol metabolism in the first year of treatment.

Androgen deprivation therapy improves the in vitro capacity of high-density lipoprotein (HDL) to receive cholesterol and other lipids in patients with prostate carcinoma

BackgroundAndrogen deprivation therapy (ADT) is widely used in the treatment of testosterone-dependent prostate carcinomas. ADT often increases plasma LDL and HDL cholesterol and triglycerides. The aim was to test whether ADT changes the transfer of lipids to HDL, an important aspect of this metabolism and HDL protective functions, and related parameters.MethodsSixteen volunteers with advanced prostate carcinoma submitted to pharmacological ADT or orchiectomy had plasma collected shortly before and after 6 months of ADT. In vitro transfer of lipids to HDL was performed by incubating plasma with donor emulsion containing radioactive lipids by 1 h at 37 °C. After chemical precipitation of apolipoprotein B-containing lipoprotein, the radioactivity of HDL fraction was counted.ResultsADT reduced testosterone to nearly undetectable levels and markedly diminished PSA. ADT increased the body weight but glycemia, triglycerides, LDL and HDL cholesterol, HDL lipid composition and CETP concentration were unchanged. However, ADT increased the plasma unesterified cholesterol concentration (48 ± 12 vs 56 ± 12 mg/dL, p = 0.019) and LCAT concentration (7.15 ± 1.81 vs 8.01 ± 1.55μg/mL, p = 0.020). Transfer of unesterified (7.32 ± 1.09 vs 8.18 ± 1.52%, p < 0.05) and esterified cholesterol (6.15 ± 0.69 vs 6.94 ± 1.29%, p < 0.01) and of triglycerides (6.37 ± 0.43 vs 7.18 ± 0.91%, p < 0.001) to HDL were increased after ADT. Phospholipid transfer was unchanged.ConclusionIncrease in transfer of unesterified and esterified cholesterol protects against cardiovascular disease, as shown previously, and increased LCAT favors cholesterol esterification and facilitates the reverse cholesterol transport. Thus, our results suggest that ADT may offer anti-atherosclerosis protection by improving HDL functional properties. This could counteract, at least partially, the eventual worse effects on plasma lipids.

Subclinical Hyperthyroidism: Status of the Cholesterol Transfers to HDL and Other Parameters Related to Lipoprotein Metabolism in Patients Submitted to Thyroidectomy for Thyroid Cancer.

Purpose: Lipid metabolism has been poorly explored in subclinical hyperthyroidism. The aim was to examine the effects of exogenous subclinical hyperthyroidism in women under levothyroxine treatment upon plasma lipids and aspects of HDL metabolism.Methodology: Ten women were studied in euthyroidism and again in exogenous subclinical hyperthyroidism. Thyroid function tests and plasma lipids were studied.Results: HDL-cholesterol (increased 21.6%, p = 0.0004), unesterified cholesterol (increased 12.3%, p = 0.04) and Lp(a) (increased 33,3%, P = 0.02) plasma concentrations were higher in subclinical hyperthyroidism compared to euthyroidism, but total cholesterol, LDL, non-HDL cholesterol, triglycerides, apo A-I, apo B were unchanged. PON1 activity (decreased 75%, p = 0.0006) was lower in subclinical hyperthyroidism. There were no changes in HDL particle size, CETP and LCAT concentrations. The in vitro assay that estimates the lipid transfers to HDL showed that esterified cholesterol (increased 7.1%, p = 0.03), unesterified cholesterol (increased 7.8%, p = 0.02) and triglycerides (increased 6.8%, p = 0.006) transfers were higher in subclinical hyperthyroidism. There were no changes in phospholipid transfers to HDL in subclinical hyperthyroidism.Conclusions: Several alterations in the plasma lipid metabolism were observed in the subclinical hyperthyroidism state that highlight the importance of this aspect in the follow-up of those patients. The increase in HDL-C and in the transfer of unesterified and esterified cholesterol to HDL, an important anti-atherogenic HDL function are consistently protective for cardiovascular health. The increase in Lp(a) and the decrease in PON-1 activity that are important risk factors were documented here in subclinical hyperthyroidism and these results should be confirmed in larger studies due to great data variation but should not be neglected in the follow-up of those patients.

The association of genetic variants in the cholesteryl ester transfer protein gene with hemostatic factors and a first venous thrombosis

BackgroundCholesteryl ester transfer protein (CETP) plays an important role in lipoprotein metabolism. Previous studies have suggested that the CETP TaqI B1/B2 allele is associated with the risk of venous thrombosis (VT). AimTo investigate the associations between genetically determined CETP concentrations and 22 hemostatic factors in healthy individuals, and the risk of a first VT event, in a large VT case‐control study. MethodsAnalyses were performed in the Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis (MEGA) case‐control study. CETP unweighted/weighted genetic risk scores (GRSs) were derived from three single‐nucleotide polymorphisms that were identified from a recent genome‐wide association study on serum CETP concentrations. The associations between CETP GRSs and 22 hemostatic factors (procoagulant/anticoagulant and fibrinolytic factors) were assessed by linear regression from an additive model in controls (n = 2813). The associations between CETP GRSs and the risk of a first VT were assessed by logistic regression analyses in 3950 VT cases and 4765 controls. ResultsIn the controls (median age, 49 years; 53% women), both unweighted and weighted GRSs showed that factor VII activity was negatively associated with the genetically determined CETP concentration (weighted GRS β –3.08 IU/dL per μg/mL genetically determined CETP, 95% confidence interval −5.73 to −0.42). No association was observed with the risk of a first VT. ConclusionsGenetically determined CETP concentrations only showed a weak negative association with factor VII activity. However, this did not lead to an association with the risk of a first VT.

Genetically-determined CETP concentration decreases large HDL and increases small VLDL without affecting LDL

Genetically-determined CETP concentration decreases large HDL and increases small VLDL without affecting LDL

No association between CETP concentration and intima media thickness in the general population: The Neo study

No association between CETP concentration and intima media thickness in the general population: The Neo study

LPS reduces hepatic CETP expression by mature resident macrophages

Aim: The potent endotoxin lipopolysaccharide (LPS) increases plasma HDL-C, the well-documented anti-inflammatory lipoprotein, accompanied with a decrease in plasma CETP concentration. Albeit that the underlying mechanism is still obscure, we recently showed that hepatic macrophages are the principal source of plasma CETP (Wang, Hepatology 2015). In this study, we investigated the role of hepatic macrophages in the mechanism by which LPS reduces plasma CETP.

The Brassica epithionitrile 1-cyano-2,3-epithiopropane triggers cell death in human liver cancer cells in vitro.

Glucosinolates are secondary metabolites present in Brassica vegetables. Alkenyl glucosinolates are enzymatically degraded forming nitriles or isothiocyanates, but in the presence of epithiospecifier protein, epithionitriles are released. However, studies on the occurrence of epithionitriles in Brassica food and knowledge about their biological effects are scarce. Epithionitrile formation from glucosinolates of seven Brassica vegetables was analyzed using GC-MS and HPLC-DAD. Bioactivity of synthetic and plant-derived 1-cyano-2,3-epithiopropane (CETP) - the predominant epithionitrile in Brassica vegetables - in three human hepatocellular carcinoma (HCC) cell lines and primary murine hepatocytes was also evaluated. The majority of the Brassica vegetables were producers of nitriles or epithionitriles as hydrolysis products and not of isothiocyanates. For example, Brussels sprouts and savoy cabbage contained up to 0.8 μmol CETP/g vegetable. Using formazan dye assays, concentrations of 380-1500 nM CETP were observed to inhibit the mitochondrial dehydrogenase activity of human HCC cells without impairment of cell growth. At 100-fold higher CETP concentrations, cell death was observed. Presence of plant matrix increased CETP-based toxicity. These in vitro data provide no indication that epithionitriles will severely affect human health by Brassica consumption. In contrast to isothiocyanates, no evidence of selective toxicity against HCC cells was found.

Alterations in lipid transfers to HDL associated with the presence of coronary artery disease in patients with type 2 diabetes mellitus.

BackgroundWe previously showed that unesterified-cholesterol transfer to high-density lipoprotein (HDL), a crucial step in cholesterol esterification and role in reverse cholesterol transport, was diminished in non-diabetic patients with coronary artery disease (CAD). The aim was to investigate whether, in patients with type 2 diabetes mellitus (T2DM), the occurrence of CAD was also associated with alterations in lipid transfers and other parameters of plasma lipid metabolism.MethodsSeventy-nine T2DM with CAD and 76 T2DM without CAD, confirmed by cineangiography, paired for sex, age (40–80 years), BMI and without statin use, were studied. In vitro transfer of four lipids to HDL was performed by incubating plasma of each patient with a donor emulsion containing radioactive lipids during 1 h at 37 °C. Lipids transferred to HDL were measured after chemical precipitation of non-HDL fractions and the emulsion. Results are expressed as % of total radioactivity of each lipid in HDL.ResultsIn T2DM + CAD, LDL-cholesterol and apo B were higher than in T2DM. T2DM + CAD also showed diminished transfer to HDL of unesterified cholesterol (T2DM + CAD = 7.6 ± 1.2; T2DM = 8.2 ± 1.5 %, p < 0.01) and of cholesteryl-esters (4.0 ± 0.6 vs 4.3 ± 0.7, p < 0.01). Unesterified cholesterol in the non-HDL serum fraction was higher in T2DM + CAD (0.93 ± 0.20 vs 0.85 ± 0.15, p = 0.02) and CETP concentration was diminished (2.1 ± 1.0 vs 2.5 ± 1.1, p = 0.02). Lecithin-cholesterol acyltransferase activity, HDL size and lipid composition were equal.ConclusionReduction in T2DM + CAD of cholesterol transfer to HDL may impair cholesterol esterification and reverse cholesterol transport and altogether with simultaneous increased plasma unesterified cholesterol may facilitate CAD development in T2DM.

Study of the impact of trans fatty acids from ruminants on blood lipids and other cardiovascular risk factors in women

The purpose of this study was to investigate the effects of dietary rTFA on plasma LDL-C, HDL-C and other cardiovascular disease risk factors in women covering a wide range of LDL-C values. In a double-blind, randomized controlled crossover study, 61 healthy women aged 19 to 70 years, LDL-C ranging from 1.6 to 5.5 mmol/l were fed two isoenergetic diets lasting 4 weeks each: 1- high in rTFA (4.8 g/2500 kcal, 1.7% of daily energy) and 2- a control diet low in rTFA (1.7 g/2500 kcal, 0.6% energy). Intake of rTFA had no impact on blood pressure, total plasma cholesterol, LDL-C, apolipoprotein B-100, B-48 and A-I and TG levels but was associated with a small yet significant reduction in plasma HDL-C concentrations compared with the control diet (1.64 ± 0.37 vs. 1.69 ± 0.37 mmol/l, −2.8%, P=0.004). There was no change in the apoB/AI ratio whereas the total C/HDL-C ratio showed a small but almost significant increase after the rTFA diet (+2.1%, P=0.053). rTFA had no impact on plasma CETP concentrations and multivariate analyses indicated that only baseline alcohol consumption predicted the change in plasma HDL-C with dietary rTFA. These results indicate that high intakes of dietary rTFA may have a small HDL-lowering effect in women. The cardiovascular impact of such change is unsure, given the magnitude of the change in HDL and the lack of change in all other risk factors. Financial support: Dairy Farmers of Canada, Provigo/Loblaws

CETP IN RARE DYSLIPIDEMIAS

Objective: To determines CETP mass and activity in rare disorders of HDL metabolism. Methods: Patients: Fasting plasma samples were obtained from two individuals with TD and from patients with LCAT deficiency, analphalipoproteinemia, Hepatic lipase deficiency (HL), vasculitis, and hypoalphalipoprteinemia. Their clinical and laboratory findings have been previously reported. Assay: CETP activity was measured using commercial CETP Fluorescence kit (Roar Biomedical Inc., New York, NY). The kit includes donor (without apoA-I) and acceptor lipoprotein particles. Incubation of donor and acceptor with a CETP source results in the CETP mediated transfer of fluorescent neutral lipid from donor to acceptor, rate of which is determined by the increase in fluorescence intensity as the fluorescent neutral lipid is removed from the donor to the acceptor. The amount of fluorescent substrate transferred was expressed as pmoles of fluorescent substrate transferred within 3 hours. CETP concentration was measured by ELISA using specific rabbit antibody against human CETP. Results: While CETP mass correlated with serum HDL-C levels, the activity decreased in patients with LCAT deficiency, FED, HL deficiency and vascultis, but increased in TD. We speculate that the composition of HDL particles in these disorders differs and results in the different CE transfer rates. Conclusion: CETP mass correlates with the HDL-C concentration but the activity differ widely among the patients with rare disorders of HDL metabolism, probably due to the changes in HDL quality.

Genotype of the mutant LDL receptor allele is associated with LDL particle size heterogeneity in familial hypercholesterolemia

Small, dense LDL particles have been associated with an increased risk of coronary artery disease. In order to assess the potential contribution of the genotype of the LDL receptor to LDL particle size heterogeneity in familial hypercholesterolemia (FH), we examined the electrophoretic characteristics of LDL particles in a large cohort of FH heterozygotes and controls. A total of 259 FH heterozygotes and 208 controls participated in the study. FH subjects were carriers of one of the nine French Canadian mutations in the LDL receptor gene. LDL particles were characterized by polyacrylamide gradient gel electrophoresis following a 6-week lipid-lowering drug-free baseline period. LDL–peak particle diameter (LDL–PPD), representing the most abundant LDL particle subpopulation, was significantly smaller in FH heterozygotes carrying a negative-receptor mutation than in subjects carrying a defective-receptor mutation (negative-receptor = 257.3 ± 4.1 Å versus defective-receptor = 259.0 ± 4.3 Å, p = 0.0006). No significant difference in plasma CETP concentrations was found between these two genotypic groups. Moreover, compared with controls having low triglyceride levels, negative-receptor subjects with high triglyceride levels had a relative risk of 19.6 ( p < 0.0001) of having small, dense LDL particles while this risk was not significantly increased among defective-receptor subjects. Multivariate analysis showed that the LDL receptor status accounted for 5.7% of the variance in the LDL–PPD after adjustment for covariates. These results suggest that the genotype of the mutant LDL receptor allele was independently associated with variations in LDL–PPD and could partly explain why negative-receptor FH heterozygotes may be at greater risk of cardiovascular disease than defective-receptor FH subjects.

Apolipoprotein L-I is positively associated with hyperglycemia and plasma triglycerides in CAD patients with low HDL

Apolipoprotein L-I (apoL-I) is present on a subset of HDL particles and is positively correlated with plasma triglycerides (TGs). We measured plasma apoL-I levels in coronary artery disease (CAD) subjects with low HDL who were enrolled in an angiographic CAD prevention trial. At baseline, apoL-I levels (n = 136; range, 2.2-64.1 mug/ml) were right skewed with a large degree of variability. Multivariate analysis for biological determinants of apoL-I revealed that the log of VLDL-TG (+0.17; P < 0.05) and hyperglycemia (HG; +0.26; P < 0.005) independently predicted apoL-I level. Hyperglycemic patients (n = 24) had mean apoL-I levels >50% higher than normoglycemic subjects (n = 112; 13.2 vs. 8.3 mug/ml, respectively; P < 0.001). No relationship between apoL-I level and change in CAD was found (r = 0.06, P = 0.49). Simvastatin-niacin therapy did not alter apoL-I levels (n = 34; P = 0.27), whereas antioxidant vitamins alone increased apoL-I by >50% (n = 36; P < 0.01). Genotyping of a known apoL-I polymorphism (Lys166Glu) did not independently account for any of the variability in apoL-I levels. In conclusion, we found TG and HG to be the strongest predictors of apoL-I within a dyslipidemic CAD population. These data provide further characterization of the novel HDL-associated apoL-I.

Estimation of multilocus haplotype effects using weighted penalised log-likelihood: analysis of five sequence variations at the cholesteryl ester transfer protein gene locus.

Direct analyses of haplotype effects can be used to identify those specific combinations of alleles that are associated with a specific phenotype. We introduce a method for direct haplotype analysis that solves two problems that arise when haplotypes are analysed in populations of unrelated subjects. Instead of assigning a single, most likely, haplotype pair to multiple heterozygous subjects, all haplotype pairs compatible with their genotype were determined and the posterior probabilities of these pairs were calculated using Bayes' theorem and estimated haplotype frequencies. For the individual patients, all possible haplotype pairs were included in the statistical analysis using the posterior probabilities as weights, which were re-estimated in an iterative process together with the haplotype effects. The second problem of unstable haplotype effect estimates, due to the numerous haplotypes and the low frequency at which some occur, was solved by assuming that haplotypes sharing the same alleles show a similar effect and that the extent of this similarity relates to the number of alleles shared. These assumptions were incorporated in a weighted log-likelihood model by introducing a penalty, where differences in effects of similar haplotypes were penalised. Using CETP gene haplotypes, consisting of five closely linked polymorphisms, and baseline CETP and HDL-C concentrations from the REGRESS population, we demonstrated that the model resulted in more stable effects than estimates based on unambiguous patients only.

Haplotype analysis of the CETP gene: not TaqIB, but the closely linked -629C-&gt;A polymorphism and a novel promoter variant are independently associated with CETP concentration

Haplotype analysis of the CETP gene: not TaqIB, but the closely linked -629C-&gt;A polymorphism and a novel promoter variant are independently associated with CETP concentration

Plasma cholesterol and CETP concentrations are lowered by dietary phytosterol ester but only the cholesterol variation related to the CETP 1405V polymorphism

Nutritional products containing fat-soluble phytosterol esters for serum cholesterol lowering have traditionally been oil-based. Their cholesterol-lowering efficacy when provided by low-fat vehicles with a diet of normal fat content is questionable. The aims of the present study were to find out whether 1-week consumption of plant stanol esters in pastilles alters absorption percentage of labeled esterified and free cholesterol and fecal elimination of sterols, including phytosterols (n = 9), and to define the impact of dietary fat on intestinal sterol ester hydrolysis (n = 8) in colectomized human subjects.Levels of lipoprotein cholesterol and triacylglycerols, non-cholesterol sterols and squalene in serum, neutral sterols, non-cholesterol sterols, fat and bile acids in feces, cholesterol absorption efficiency and cholesterol synthesis were analyzed at baseline and at the end of the treatment period. Analyses of esterified and free cholesterol and phytosterols were performed during diets with normal and low-fat content.Serum levels of total and low-density lipoprotein cholesterol decreased by 9% and 14%, respectively (P < 0.01 for both), and absorption of 3H-esterified and 14C-free cholesterol decreased in proportion to baseline values (r = −0.58, P < 0.05) by over 40% (P < 0.01) in colectomized patients with stanol ester pastilles. Fecal elimination of cholesterol was increased by about 35% and almost 60% of campestanol and sitostanol esters were hydrolyzed during their transit in gastrointestinal tract when consumed with a normal fat diet (mean daily fat 93 ± 13 g) for 1 week. The hydrolysis of plant stanol esters was more pronounced with a normal than with a low-fat diet (70% versus 40%, P < 0.001).We conclude that plant stanol esters provided in fat free milieu exert favourable effects on serum lipid profile by decreasing absorption of cholesterol in colectomized human subjects, even though the intestinal hydrolysis of plant stanol esters is weaker on low than normal fat diet.

CETP concentration is not modified but PLTP activity is increased and correlates negatively with plasma HDL-C levels in the elderly

CETP concentration is not modified but PLTP activity is increased and correlates negatively with plasma HDL-C levels in the elderly