Changes In Plasma Lipoprotein Profiles Research Articles

Liver-specific ablation of HNF-4α in mice is associated with changes in plasma lipoprotein profiles and the expression of genes involved in lipoprotein metabolism

Liver-specific ablation of HNF-4α in mice is associated with changes in plasma lipoprotein profiles and the expression of genes involved in lipoprotein metabolism

The effect of N-stearoylethanolamine on plasma lipid composition in rats with experimental insulin resistance

A model of insulin resistance (IR), induced by prolonged high fat diet with high content of saturated fats was used to investigate the effect of N-stearoylethanolamine (NSE) on the composition of free fatty acids (FFA), plasma lipoprotein spectrum and content of proinflammatory cytokine TNFα in rats. The results of this work showed a rise in the content of monounsaturated fatty acids (18:1 n-9) and a reduction in the level of polyunsaturated fatty acids (20:4 n-6) in plasma of rats with experimental IR. These findings are accompanied by the increased TNFα production and significant changes in plasma lipoprotein profile of rats with the fat overload. Particularly, a decreased high-density lipoprotein (HDL) cholesterol level and increased low-density (LDL) and very low-density lipoprotein (VLDL) cholesterol level were detected. The NSE administration to obese rats with IR restored the content of mono- and polyunsaturated FFA, increased HDL cholesterol content and reduced LDL cholesterol level. In addition, the IR rats treated with NSE showed normalization in the serum TNFα level. Our results showed the restoration of plasma lipid profile under NSE administration in rats with obesity-induced IR. Considering the fact that plasma lipid composition displays the lipid metabolism in general, the NSE actions may play a significant role in the prevention of IR-associated complications.

P1.038 Chlamydial Antigen and Nucleic Acid Detection in Liver Biopsies from Patients with Chronic Cholelithiasis

Background It is known that chlamydial species can propagate in hepatocyte cell lines. Moreover, some clinical cases of chlamydial infection involve liver abnormalities. This study was to clarify whether chlamydial markers (protein and nucleic acids) could be detected in liver biopsies from patients with calculous cholecystitis. Material and Methods Liver biopsies were obtained from 39 patients during cholecystectomy and analysed with immunohistochemical, nucleic acid amplification and serological protocols. Liver specimens from 8 trauma victims served as controls. Results It was shown that from 39 patients with cholecystitis 19 gave considerable signal generated by antibodies against C. trachomatis (15 patients) or C. pneumoniae (4 patients). 10.2% (4/39) of the samples contained detectable 16S rRNA genomic sequence from C. pneumoniae while amplifiable fragments of 16S rRNA and pLGV cryptic plasmid from C. trachomatis were found in 20.5% (8/39) of DNA specimens. The control group had a zero detection rate for chlamydial genetic markers in the liver. Simultaneous detection of genetic and immunohistochemical markers validated by positive serological status took place in a very limited number of the patients (4 cases for C. trachomatis and 2 cases for C. pneumoniae). Moreover, it was shown that C. trachomatis and C. pneumoniae can efficiently propagate in freshly isolated rat primary hepatocytes forming infectious progeny. Conclusions Identification of chlamydial markers in liver biopsies along with the ability of the chlamydial pathogens to propagate in native hepatocytes may suggest the possible involvement of chlamydial species in inflammatory hepatobiliary disease. We have assumed previously that abnormalities of cholesterol homeostasis associated with the increase of ApoB-containing lipoproteins may promote enhanced uptake of chlamydial particles in the liver. Thus, it is conceivable that the appearance of chlamydial markers in hepatic biopsies of patients with cholelithiasis takes place due to proatherogenic changes in plasma lipoprotein profile.

Dietary Calcium Decreases Plasma Cholesterol Level only in Female but not in Male Hamster Fed a High Cholesterol Diet

ObjectiveTo investigate the effect of dietary calcium on plasma lipoprotein profile in castrated and ovariectomized hamsters. MethodsMale, castrated, female and ovariectomized hamsters (n=36 each group) were randomly divided into three sub-groups (n=12) and fed one of the three diets containing 0, 2, and 8 g calcium per kg diet for a period of six weeks. Changes in plasma lipoprotein profile were monitored at the end of week 0, 3 and 6. ResultsPlasma total cholesterol (TC), non-high density lipoprotein cholesterol (non-HDL-C), triacylglycerols (TG) and TC/HDL-C were decreased only in intact female and ovariectomized hamsters. In contrast, three levels of dietary calcium had no effect on lipoprotein profiles in both intact male and castrated hamsters. ConclusionBeneficial modification of lipoprotein profile by dietary calcium was gender-dependent at least in hamsters.

Efecto del consumo de tres huevos de gallina diarios sobre el perfil lipídico en pacientes dislipidémicos

Introduction Although limiting consumption of chicken eggs is recommended to avoid increased plasma cholesterol, there is no definitive evidence to support this recommendation. The aim of this study was to evaluate changes in plasma lipoprotein profile in Cuban patients consuming an egg-rich diet. Methods We studied eight patients recruited from the Lipids Clinic of the Hermanos Ameijeiras Hospital (Cuba). After 6 weeks on an antilipidemic diet, the patients ate three whole eggs daily for 3 months. Lipid profiles were studied at baseline, and at 6 and 12 weeks. Results The only significant changes were an increase in low-density lipoprotein-cholesterol (LDLc) and high-density lipoprotein-cholesterol (HDLc) levels at 6 weeks vs baseline levels. However, triglycerides, total cholesterol, non-HCL-cholesterol, and the total cholesterol/HDLc ratio showed no change at 6 and 12 weeks vs baseline levels. Interindividual changes in lipid profile were observed, probably because of the individual regulation of cholesterol metabolism after a diet rich in eggs. Conclusions Eggs are a nutritionally complete food. Consequently, consumption of other cholesterol-rich foods should be reduced, in addition to that of egg consumption, before identifying lipoprotein metabolism status in each patient.

HDL and immunomodulation: an emerging role of HDL against atherosclerosis

Changes in plasma lipoprotein profiles, particularly low levels of high-density lipoprotein (HDL) cholesterol, are associated with several inflammatory and immune diseases, including atherosclerosis and rheumatoid arthritis, implying the potential link between HDL and immunity. Accumulating evidence suggests that HDL possesses anti-inflammatory effects and has an important function in host defense as part of the innate immune system. In addition, HDL inhibits the ability of antigen-presenting cells (APCs) to stimulate T cells. It is subsequently discovered that HDL or HDL-associated platelet-activating factor-acetylhydrolase can restore the emigratory process of monocyte-derived dendritic cells and thus result in resolution of inflammatory reactions in atherosclerotic plaques. Lipid rafts in plasma membrane are the key structure responsible for the immunomodulation effects of HDL, the remarkable ability of HDL to regulate innate and adaptive immune responses extends our understanding of its atheroprotective role, and provides new therapeutic approaches to atherosclerosis and other inflammatory conditions.

Retracted: Genistein improves liver function and attenuates non‐alcoholic fatty liver disease in a rat model of insulin resistance

The high fructose-fed rat is widely used as a model of insulin resistance. Genistein, a soy isoflavone, has been shown to improve insulin sensitivity in this model. The present study investigated whether genistein could prevent fatty liver disease in this model. Male Wistar rats were fed a diet containing starch (control) or 60% fructose (insulin-resistant model). Fifteen days later, rats in each dietary group were divided into two groups and were treated with either genistein (1 mg/kg per day) in dimethylsulfoxide (DMSO) or 30% DMSO alone. After 60 days, markers of liver injury, oxidative stress, interleukin (IL)-6, tumor necrosis factor (TNF)-α, lipids, lipoprotein profile, nitrite, and nitrosothiol in the plasma and liver were quantified. Liver sections were examined for 3-nitrotyrosine (3-NT) expression and pathological lesions. Fructose-fed rats displayed hyperlipidemia, significant changes in plasma lipoprotein profile, and increases in IL-6 and TNF-α levels compared with control. In addition, the accumulation of lipids, liver injury, a decline in liver function, inactivation of the glyoxalase system, depletion of antioxidants, and increased 3-NT expression were observed in the fructose-fed group. Administration of genistein to fructose-fed rats significantly reduced these biochemical and histological abnormalities. Genistein activates the antioxidant profile, decreases IL-6 and TNF-α concentrations, prevents oxidative damage, and ameliorates fatty liver in insulin-resistant rats.

Effects of cardiovascular lifestyle change on lipoprotein subclass profiles defined by nuclear magnetic resonance spectroscopy

BackgroundLow-density lipoprotein (LDL) cholesterol lowering is a primary goal in clinical management of patients with cardiovascular disease, but traditional cholesterol levels may not accurately reflect the true atherogenicity of plasma lipid profiles. The size and concentration of lipoprotein particles, which transport cholesterol and triglycerides, may provide additional information for accurately assessing cardiovascular risk. This study evaluated changes in plasma lipoprotein profiles determined by nuclear magnetic resonance (NMR) spectroscopy in patients participating in a prospective, nonrandomized lifestyle modification program designed to reverse or stabilize progression of coronary artery disease (CAD) to improve our understanding of lipoprotein management in cardiac patients.ResultsThe lifestyle intervention was effective in producing significant changes in lipoprotein subclasses that contribute to CAD risk. There was a clear beneficial effect on the total number of LDL particles (-8.3%, p < 0.05 compared to matched controls), small dense LDL particles (-9.5%, p < 0.05), and LDL particle size (+0.8%; p < 0.05). Likewise, participants showed significant improvement in traditional CAD risk factors such as body mass index (-9.9%, p < 0.01 compared to controls), total cholesterol (-5.5%, p < 0.05), physical fitness (+37.2%, p < 0.01), and future risk for CAD (-7.9%, p < 0.01). Men and women responded differently to the program for all clinically-relevant variables, with men deriving greater benefit in terms of lipoprotein atherogenicity. Plasma lipid and lipoprotein responses to the lifestyle change program were not confounded by lipid-lowering medications.ConclusionIn at risk patients motivated to participate, an intensive lifestyle change program can effectively alter traditional CAD risk factors and plasma lipoprotein subclasses and may reduce risk for cardiovascular events. Improvements in lipoprotein subclasses are more evident in men compared to women.

Phytosterol-mediated inhibition of intestinal cholesterol absorption is independent of ATP-binding cassette transporter A1

An increased activity of ATP-binding cassette transporter (ABC) A1 has been proposed as a mechanism underlying the hypocholesterolaemic effect of phytosterols. In the present study, ABCA1-deficient mice (ABCA1-/- mice) were used to examine the involvement of the ABCA1 in the reduction of intestinal cholesterol absorption in response to a phytosterol-enriched diet. A decrease in intestinal cholesterol absorption of 39 and 35 % was observed after phytosterol treatment in ABCA1+/+ mice and in ABCA1-/- mice, respectively. No statistically significant changes in plasma lipoprotein profile or in intestinal ABCG5, ABCG8 and Niemann-Pick C1-Like 1 gene expression levels were found when phytosterol-treated ABCA1-/- mice and untreated ABCA1-/- mice were compared. We conclude that phytosterol inhibition of cholesterol absorption in mice is independent of ABCA1.

Expression of the Pregnane X Receptor in Mice Antagonizes the Cholic Acid–Mediated Changes in Plasma Lipoprotein Profile

Modification of lipoprotein metabolism by bile acids has been mainly explained by activation of the farnesyl X receptor (FXR). The aim of the present study was to determine the relative contribution of the pregnane X receptor (PXR), another bile acid-activated nuclear receptor to changes in plasma lipoprotein profile. Wild-type mice, Pxr-deficient mice, and Pxr-null mice expressing human PXR (Pxr-null SXR-Tg mice) were fed a cholic acid-containing diet, and consequences on plasma lipoprotein profiles and target gene expression were assessed. Cholic acid produced significant decreases in high-density lipoprotein (HDL) cholesterol, plasma apolipoprotein (apo)A-I and hepatic apoA-I mRNA in wild-type mice. Interestingly, the effect of cholic acid was significantly more pronounced in Pxr-deficient mice, indicating that PXR contributes to the weakening of the effect of bile acids on lipoprotein metabolism. Reciprocally, changes in HDL/apoA-I profiles were abolished in Pxr-null SXR-Tg mice in which PXR-responsive genes, particularly those involved in bile acid detoxification were readily activated after cholic acid treatment. PXR expression in mice antagonizes the cholic acid-mediated downregulation of plasma HDL cholesterol and apoA-I, and magnification of PXR/SXR-mediated changes may constitute a new mean to counteract the effects of bile acids on plasma lipoproteins.

Differences in the Lipoprotein Binding profile of Halofantrine in Fed and Fasted Human or beagle Plasma are dictated by the Respective Masses of Core Apolar Lipoprotein Lipid

Halofantrine hydrochloride (Hf) is an orally active, highly lipophilic antimalarial indicated for the treatment of multi-drug resistant Plasmodium falciparum. In this study, we have examined the binding profile of Hf to the various classes of human and beagle plasma lipoproteins as such interactions have been implicated in a post-prandial plasma lipoprotein-induced decrease in the total clearance and volume of distribution of Hf. The distribution of Hf within plasma was dominated by interaction with the various classes of plasma lipoproteins, and the characteristics and extent of binding were markedly different between species and between pre- and post-prandial plasma. In an attempt to understand the basis for the differential binding of Hf to the various lipoprotein fractions, the relationship between the proportion of Hf associated with each lipoprotein fraction (as a function of the respective mass of protein, triglyceride, cholesterol, and phospholipid) was investigated. The data indicated that the distribution of Hf between plasma lipoproteins was highly correlated with the apolar lipid load of individual plasma lipoprotein fractions suggesting that the mechanism of association was primarily via solubilization in the lipoprotein apolar lipid core. These data suggest that acute changes in plasma lipoprotein profiles, such as encountered post-prandially or in disease states such as malaria, will likely have an impact on the plasma lipoprotein binding of Hf.

Effects of hormone replacement therapy on cardiovascular risk factors in postmenopausal women

Objective: To investigate changes in plasma lipoprotein profile, hemostatic factors, platelet aggregation, endothelin-1, and cardiac function during postmenopausal sequential 6-month hormone replacement therapy (HRT). Design: Open longitudinal prospective study. Setting: Gynecologic department of a medical center. Patient(s): Twenty-one healthy nonhysterectomized postmenopausal women. Intervention(s): Oral E 2 valerate (2 mg/d) combined with medroxyprogesterone acetate (MPA) (10 mg/d) during the last 10 days of each 21-day cycle. The treatment period was 6 months. Main Outcome Measure(s): Plasma lipoprotein profile, hemostatic parameters, platelet aggregation, endothelin-1, and left ventricular function. Result(s): After 6 months of treatment, total cholesterol, triglyceride, and low-density lipoprotein (LDL) cholesterol were significantly progressively reduced. Atherogenic indices of total cholesterol-to-high-density lipoprotein (HDL) cholesterol and LDL-to-HDL cholesterols also showed a significant progressive decline. The concentrations of antithrombin III were significantly increased. The maximum aggregation and slope of platelet aggregation were significantly reduced, but all parameters were more pronounced at I month of HRT than at 3 or 6 months. The concentrations of endothelin-1 were significantly reduced (by 16.1%). In the evaluation of left ventricular function, only peak atrial diastolic velocity was significantly reduced. Conclusion(s): Combined HRT had favorable effects on lipids and lipoproteins, hemostatic factors, platelet aggregation, endothelin-1, and left ventricular function. However, further study is needed to evaluate the long-term effects of combined HRT, especially on platelet aggregation and cardiac function.

Alternative Splicing of the Human Cholesteryl Ester Transfer Protein Gene in Transgenic Mice: EXON EXCLUSION MODULATES GENE EXPRESSION IN RESPONSE TO DIETARY OR DEVELOPMENTAL CHANGE

The plasma cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl ester from high density lipoprotein to other lipoproteins. The human DETP gene produces two forms of mRNA, with or without exon 9 (E9)-derived sequences. To study the function and regulation of alternative splicing the CETP gene, transgenic mice were prepared 1) with the metallothionein (mT) promoter driving an E9-deleted construct (mT.CETP(-E9) transgene), and 2) with the natural flanking regions (NFR) controlling expression of genomic sequences which permit alternative splicing of E9 (NFR.CETP(+/-E9) transgene). With zinc induction, the mT.CETP(-E9) transgene gave rise to abundant E9-deleted CETP mRNA in liver and small intestine, but only relatively small amounts of E9-deleted protein were found in plasma. The E9-deleted form of CETP was inactive in lipid transfer and produced no changes in plasma lipoprotein profile. The NFR.CETP(+/-E9) transgene gave rise to full-length (FL) and E9-deleted forms of CETP mRNA in liver and spleen. In response to hypercholesterolemia induced by diet and breeding into an apoE gene knock-out background, the FL CETP mRNA was induced more than the E9-deleted mRNA, resulting in a 2-fold increase in ratio of FL/E9-deleted mRNA. The expression of CETP mRNA was found to be developmentally regulated. In NFR.CETP(+/-E9) transgenic mice CETP mRNA levels were markedly increased in the liver and small intestine in the perinatal period and decreased in adult mice, whereas CETP mRNA in the spleen was low in perinatal mice and increased in adults. The developmental increase in CETP mRNA in the liver and spleen was preceded by an increased ratio of FL/E9-deleted forms. Thus, the E9-deleted mRNA appears to be poorly translated and/or secreted, and the cognate protein is inactive in lipid transfer and lipoprotein metabolism. CETP gene expression was found to be highly regulated in a tissue-specific fashion during development. Increased CETP gene expression during development or in response to hypercholesterolemia is associated with preferential accumulation of the full-length CETP mRNA.

Diurnal variation in cyclosporine kinetics.

Venkataramanan, Raman*; Yang, Shuin†; Burckart, Gilbert J.*; Ptachcinski, Richard J.*; Van Thiel, David H.‡; Starzl, Thomas E.† Author Information