Hypercholesterolemia,low density lipoprotein receptor and proprotein convertase subtilisin/kexin-type 9

Atherosclerotic cardiovascular disease is the main cause of mortality and morbidity in the world. Plasma levels of low density lipoprotein cholesterol （LDL-C） are positively correlated with the risk of atherosclerosis. High plasma LDL concentrations in patients with hypercholesterolemia lead to build-up of LDL in the inner walls of the arteries, which becomes oxidized and promotes the formation of foam cells, consequently initiating atherosclerosis. Plasma LDL is mainly cleared through the LDL receptor （LDLR） pathway. Mutations in the LDLR cause familiar hyperch- olesterolemia and increase the risk of premature coronary heart disease. The expression of LDLR is regulated at the transcriptional level via the sterol regulatory element binding protein 2 （SREBP-2） and at the posttranslational levels mainly through proprotein convertase subtilisin/kexin-type 9 （PCSK9） and inducible degrader of the LDLR （IDOL）. In this review, we summarize the latest advances in the studies of PCSK9.

Effect of Curcumin on the Gene Expression of Low Density Lipoprotein Receptors

Objective： To investigate the molecular mechanisms and effective target ponits of lipid-lowering drug, Rhizoma Curcumae Longae, and study the effect of curcumin on the expression of low density lipoprotein （LDL） receptors in macrophages in mice. Methods. Macrophages in mice were treated with curcumin, which was purified from the ethanolly extraction of Rhizoma Curcumae Longae for 24 h. The LDL receptors expressed in the macrophages were determined by enzyme-linked immunosorbent assay （ELISA） and assay of Dil labeled LDL uptake by flow cytometer. Results： It was found for the first time that 10 μmol/L-50 μmol/L curcumin could obviously up-regulate the expression of LDL receptor in macrophages in mice, and a dose-effect relationship was demonstrated. Conclusion： One of the lipid-lowering mechanisms of traditional Chinese medicine, Rhizoma Curcumae Longae, was completed by the effect of curcumin through the up-regulation of the expression of LDL receptor.

Function and Significance of Very Low Density Lipoprotein Receptor Subtype Ⅱ

To explore the functions of very low density lipoprotein receptor (VLDL-R) subtype II in lipoprotein metabolism and foam cells formation, the recombinant plasmid with the two subtypes cDNA was constructed respectively, the ldl-A7 cell lines were transfected and two cell lines expressing VLDL-R were obtained: one stably expressing the VLDLR with the O-linked sugar region (type I VLDLR) and the other without the O-linked sugar region (type II VLDLR). In the study on binding of VLDLR to their nuclein labeled natural ligands (VLDL and β-VLDL), it was found that surface binding of 125I-VLDL or 125I-β-VLDL of ldl-A7 cells transfected with type I VLDLR recombinant (ldl-A7-VRI) was more higher than that of ldl-A7 cells transfected with type II VLDLR recombinant (ldl-A7-VRII). After being incubated with VLDL for different time, the contents of triglyceride and total cholesterol in cells were mensurated, and the formation of foam cells and accumulation of lipid in cells was observed by oil-red O staining. The results showed that the contents of triglyceride and total cholesterol in ldl-A7-VR I were much higher than those in ldl-A7-VR II, and ldl-A7-VR I could transform into foam cells notably. It was suggested that type I VLDLR binds with relative higher affinity to VLDL and β-VLDL, and internalizes much more lipoprotein into cells. As a result, we can conclude that type I VLDLR plays a more important role in lipoprotein metabolism and foam cells formation than type II VLDLR.

Obstructive jaundice leads to accumulation of oxidized low density lipoprotein in human liver tissue

Oxidized low density lipoprotein （ox-LDL） molecule is one of the most important modified lipoproteins produced during the oxidative stress. Modified lipoproteins have been defined as being part of the immune inflammatory mechanisms in association with oxidant stress. We have reported the accumulation of ox-LDL in Balb/c mice liver after bile duct ligation previously. Here, we investigated this finding in human beings with obstructive jaundice. Our study demonstrates that obstructive jaundice results in tremendous accumulation of ox-LDL in the liver tissue of patients.

Roles of low?density lipoproteinreceptor?related protein 1 in tumors

Low-density lipoprotein receptor-related protein 1(LRP1,also known as CD91),a multifunctional endocytic and cell signaling receptor,is widely expressed on the surface of multiple cell types such as hepatocytes,fibroblasts,neurons,astrocytes,macrophages,smooth muscle cells,and malignant cells.Emerging in vitro and in vivo evidence demonstrates that LRP1 is critically involved in many processes that drive tumorigenesis and tumor progression.For example,LRP1 not only promotes tumor cell migration and invasion by regulating matrix metalloproteinase(MMP)-2and MMP-9 expression and functions but also inhibits cell apoptosis by regulating the insulin receptor,the serine/threonine protein kinase signaling pathway,and the expression of Caspase-3.LRPI-mediated phosphorylation of the extracellular signal-regulated kinase pathway and c-jun N-terminal kinase are also involved in tumor cell proliferation and invasion.In addition,LRP1 has been shown to be down-regulated by microRNA-205 and methylation of LRP1CpG islands.Furthermore,a novel fusion gene,LRP1-SNRNP25,promotes osteosarcoma cell invasion and migration.Only by understanding the mechanisms of these effects can we develop novel diagnostic and therapeutic strategies for cancers mediated by LRP1.

Association between Low-density Lipoprotein Receptor-related Protein 5 Polymorphisms and Type 2 Diabetes Mellitus in Han Chinese:a Case-control Study

Objective To investigate the association between low-density lipoprotein receptor-related protein 5 （LRPS） variants （rs12363572 and rs4930588） and type 2 diabetes mellitus （T2DM） in Han Chinese. Methods A total of 1842 T2DM cases （507 newly diagnosed cases and 1335 previously diagnosed cases） and 7777 controls were included in this case-control study. PCR-RFLP was conducted to detect the genotype of the two single nucleotide polymorphisms （SNPs）. Odds ratios （ORs） and 95% confidence intervals （95% CIs） were calculated to describe the strength of the association by logistic regression. Results In the study subjects, neither rs12363572 nor rs4930588 was significantly associated with T2DM, even after adjusting for relevant covariates. When stratified by body mass index （BMI）, the two SNPs were also not associated with T2DM. Among the 3 common haplotypes, only haplotype ~ was associated with reduced risk of T2DM （OR 0.820, 95% CI 0.732-0.919）. In addition, rs12363572 was associated with BMI （P〈0.001） and rs4930588 was associated with triglyceride levels （P=0.043） in 507 newly diagnosed T2DM cases but not in healthy controls. Conclusion No LRP5 variant was found to be associated with T2DM in Han Chinese, but haplotype TT was found to be associated with T2DM.

Hepatitis C virus clearance and less liver damage in patients with high cholesterol, low-density lipoprotein cholesterol and APOE ε4 allele

BACKGROUND Cholesterol is related to improvements in the rate of sustained virological response and a robust immune response against the hepatitis C virus(HCV).APOE gene polymorphisms regulate cholesterol levels modifying the course of the HCV infection.The relationship between cholesterol,APOE alleles,and the outcome of HCV infection has not been evaluated in the admixed population of Mexico.AIM To investigate the role of APOE-ε2,-ε3,and-ε4 alleles and the metabolic profile in the outcome of HCV infection.METHODS A total of 299 treatment-na?ve HCV patients were included in this retrospective study.Patients were stratified in chronic hepatitis C(CHC)(n=206)and spontaneous clearance(SC)(n=93).A clinical record was registered.Biochemical tests were assessed by dry chemistry assay.APOE genotypes were determined using a Real-Time polymerase chain reaction assay.RESULTS Total cholesterol,low-density lipoprotein cholesterol(LDL-c),triglycerides,and hypercholesterolemia were higher in SC than CHC patients as well as the frequency of the APOEε4 allele(12.4%vs 7.3%).SC patients were overweight(54.8%).Theε4 allele was associated with SC(OR=0.55,95%CI:0.31-0.98,P=0.042)and mild fibrosis(F1-F2)in CHC patients(OR 0.091,95%CI 0.01-0.75,P=0.020).LDL-c≥101.5 mg/dL(OR=0.20,95%CI:0.10-0.41,P<0.001)and BMI≥26.6 kg/m2(OR=0.37,95%CI:0.18-0.76,P<0.001)were associated with SC status;while ALT≥50.5 IU/L was negatively associated(OR=5.67,95%CI:2.69-11.97,P<0.001).CONCLUSION In SC patients,the APOEε4 allele and LDL-c conferred a protective effect in the course of the HCV infection in the context of excess body weight.

Relationship between the low density lipoprotein receptor gene polymorphism and serum lipid levels in the Guangxi Bai Ku Yao population

Objectives Bai Ku Yao(White-trousers Yaos)is a special branch of Yao minority in China.They are now living in both Lihu and Baxu villages,Nandan County, Guangxi,China.The population size is about 30,000.The special customs and culture of Bai Ku Yao,including their special clothing,intra-ethnic marriages and alcohol intake are still completely conserved to the present day.In previous epidemiologic studies,we found that the serum lipid levels and the prevalence of hyperlipidaemia were lower in Bai Ku Yao than in Han Chinese from the same region.This ethnic difference in serum lipid profiles is still not well known.We hypothesized that there may be significant differences in some genetic polymorphismsssociation of low density lipoprotein receptor (LDL-R) genepolymorphism and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations.Methods A total of 1024 subjects of Bai Ku Yao and 792 participants of Han Chinese were stud- ied by a stratified randomized cluster sampling.Epidemiological survey was carried out using internationally standardized methods.Information on demographics,socioeconomic status, and lifestyle factors was collected with standardized questionnaires. The height,weight,waist circumference,blood pressure, and serum total cholesterol(TC),triglyceride(TG), high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),apolipoprotein(Apo) A1, and ApoB were measured.Body massindex(BMI,kg/m2) was calculated.Genotyping of the LDL-RAvaⅡwas performed by polymerse chain reaction and restriction fragment length polymorphism combined with gel electrophoresis,and then confirmed by direct sequencing.Results(l)The height,weight,serum TC,HDL-C,LDL-C,ApoAl levels and the ratio of ApoAl to ApoB were lower in Bai Ku Yao than in Han Chinese(P【0.01 for all),whereas the percentage of subjects who consumed alcohol or smoked cigarettes was higher in Bai Ku Yao than in Han Chinese(P【0.01 for each).(2) The frequency of A+ allele in Bai Ku Yao was 34.5%,and the frequencies of A-A-,A-A+ and A+A + genotypes were 42.6%,45.9%and 11.5%;respectively. The frequency of A+ allele in Han Chinese was 19.3%(P【0.001),and the frequencies of A-A-,A-A + and A+A+ genotypes were 64.9%,31.6%and 3.5%(P【0.001);respectively. The frequencies of A-A-,A-A+ and A+A+ genotypes in Bai Ku Yao were significant difference between males and females,between normal TC and high TC subgroup, and between normal LDL-C and high LDL-C subgroup (P【0.05 for all),whereas the frequencies of A- and A+ ? alleles in Han Chinese were significant difference between males and females(P【0.05).(3) Serum LDL-C levels in Bai Ku Yao were significant difference among the A-A-, A-A+ and A+A+ genotypes(P【0.05),the A+ carriers had higher serum LDL-C levels.Serum HDL-C levels in Han Chiese were significant difference among the A-A-,A-A + and A+A+ genotypes(P【0.01),the A+ carriers had higher serum HDL-C levels.(4) After adjusting other factors,the prevalence of LDL-C abnormality was still higher in Han Chiese than in Bai Ku Yao.The prevalence of TC abnormality in Han Chinese was almost twice high as in Bai Ku Yao. The age and diet were common risk factor for TC abnormality. No effect of AvaⅡgenotype or alcohol consumption on the TC abnormality was found,but the combination of geno-type and alcohol consumption can increase the prevalence of TC abnormality[Exp(B) =(1.154)].Age was negatively cor- related with TG level.Conclusions Serum TC and LDL-C levels were lower in Bai Ku Yao than in Han Chinese.There were significant differences in the AvaⅡallele and genotype frequencies between the he A+ carriers in Bai Ku Yao had higher serum LDL-C levels,whereas the A+ carriers in Han had higher serum HDL-C levels.Interactions between alcohol consumption or cigarette smoking and the LDL-R AvaⅡgenotype were also observed.The differences in the serum lipid profiles between the two ethnic groups might partly result from different genotypic frequency of LDL-R AvaⅡpolymorphism or differentgene-enviromental interactions.Bai Ku Yao and Han population,the frequency of A + allele was higher in Bai Ku Yao than in Han.T between the two ethnic groups.Therefore,the aim of the present study was to detect the

Antitumoral activity of low density lipoprotein-aclacinomycin complex in mice bearing H_(22) tumor

INTRODUCTIONCancer cells,which proliferate rapidly need largeamounts of cholesterol for new membrane synthesis,and high LDL receptor (LDLR) activity.LDL hasbeen proposed as a useful discriminatory vehicle forthe delivery of cytotoxic drugs to tumor cells.LDL presents many advantages as drug

Binge ethanol intake in chronically exposed rat liver decreases LDL-receptor and increases angiotensinogen gene expression

AIM: To investigated the status of low-density lipoprotein (LDL)-receptor and angiotensionogen gene expression in rats treated chronically with ethanol followed by binge administration, a model that mimics the human scenario. METHODS: Rats were chronically treated with ethanol in liquid diet for 4 wk followed by a single binge mode of ethanol administration (5 mg/kg body weight). Samples were processed 4 h after binge ethanol administration (chronic ethanol binge). Control rats were fed isocaloric diet. In the control for binge, ethanol was replaced by water. Expression of mRNA for angioten-sinogen, c-fos and LDL-receptor, and nuclear accumulation of phospho-extracellular regulated kinases (ERK)1/2 and ERK1/2 protein were examined. RESULTS: Binge ethanol administration in chronically treated rats caused increase in steatosis and necrosis. Chronic ethanol alone had negligible effect on mRNA levels of LDL-receptor, or on the levels of nuclear ERK1/2 and phospho-ERK1/2. But, chronic ethanol followed by binge caused a decrease in LDL-receptor mRNA, and also decreased the levels of ERK1/2 and phospho-ERK1/2 in the nuclear compartment. On the other hand, chronic ethanol-binge increased mRNA expression of angiotensinogen and c-fos. CONCLUSION: Binge ethanol after chronic exposure, causes transcriptional dysregulation of LDL-receptor and angiotensinogen genes, both cardiovascular risk factors.

Lipoprotein metabolism in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease （NAFLD）, an pathologies characterized by fatty accumulation in escalating health problem worldwide, covers a spectrum of hepatocytes in early stages, with potential progression to liver inflammation, fibrosis, and failure. A close, yet poorly understood link exists between NAFLD and dyslipidemia, a constellation of abnormalities in plasma lipoproteins including triglyceride-rich very low density lipoproteins. Apolipoproteins are a group of primarily liver-derived proteins found in serum lipoproteins; they not only play an extracellular role in lipid transport between vital organs through circulation, but also play an important intracellu- lar role in hepatic lipoprotein assembly and secretion. The liver functions as the central hub for lipoprotein metab- olism, as it dictates lipoprotein production and to a significant extent modulates lipoprotein clearance. Lipoprotein metabolism is an integral component of hepatocellular lipid homeostasis and is implicated in the pathogenesis, potential diagnosis, and treatment of NAFLD.

Silymarin in non alcoholic fatty liver disease

AIM: This study was undertaken to evaluate the hepatic effects of silybum marianum on non alcoholic fatty liver disease (NAFLD). METHODS: In 72 patients affected by NAFLD, main metabolic, hepatic and anti-inflammatory parameters were assayed after 3 mo of a restricted diet and before silymarin treatment (twice a day orally). The brightness of liver echography texture (hepatorenal ratio brightness) was also defined at same time. These evaluations were repeated after 6 mo of treatment. RESULTS: Serum levels of some metabolic and anti-inflammatory data nonsignificantly lowered after 6 mo of silymarin. On the contrary, Steato test, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase were significantly (P < 0.001) reduced. Instead, the AST/ALT ratio unchanged. Finally, the hepatorenal brightness ratio, as an index of hepatic steatosis, significantly (P < 0.05) dropped. CONCLUSION: The obtained results indicate that silymarin appears to be effective to reduce the biochemical, inflammatory and ultrasonic indices of hepatic steatosis. Some parameters indicative of early stage of atherosclerosis were also lowered.

Effects of Curcuma Longa on proliferation of cultured bovine smooth muscle cells and on expression of low density lipoprotein receptor in cells

Objective To investigate the inhibitory effects of aqueous turmeric extract (AqT) and serum of rats orally treated with ethanol extract of turmeric (SeT) on proliferation of vascular smooth muscle cells (VSMC) and its effects on the expression of low density lipoprotein receptor (LDL R) antigen on the surface of smooth muscle cells. Methods Enzyme linked immunosorbent assay (ELISA) for the expression of LDL R protein and thiazolyl blue (MTT) assay for the proliferation of VSMC were used in this study. Results Both aqueous turmeric extract (AqT) and serum of rats orally treated with ethanol extract of turmeric (SeT) could inhibit 10% serum activated proliferation of VSMC. The inhibition shown in both experiments was dose dependent with an inhibitory rate of 18.9% at 20 mg/ml AqT and rate of 20.1% at 10% SeT respectively. AqT up regulated the expression of LDL R protein with a highest rate at 5 mg/ml AqT in 3% lipoprotein deficient serum (LPDS). SeT did not show significant effect on the expression of LDL R on the surface of VSMC. Conclusion The extracts of turmeric may be extended to decrease the risk of atherosclerosis (AS).

Role of VLDL Receptor in the Process of Foam Cell Formation

The role of very low density lipoprotein receptor (LVLDR) in the process of foam cell formation was investigated. After the primary cultured mouse peritoneal macrophages were incubated with VLDL, β VLDL or low density lipoprotein (LDL), respectively for 24 h and 48 h, foam cells formation was identified by oil red O staining and cellular contents of triglyceride (TG) and total cholesterol (TC) were determined. The mRNA levels of LDLR, LDLR related protein (LRP) and VLDLR were detected by semi quantitative RT PCR. The results demonstrated that VLDL, β VLDL and LDL could increase the contents of TG and TC in macrophages. Cells treated with VLDL or β VLDL showed markedly increased expression of VLDLR and decreased expression of LDLR, whereas LRP was up regulated slightly. For identifying the effect of VLDL receptor on cellular lipid accumulation, ldl A7 VR cells, which expresses VLDLR and trace amount of LRP without functional LDLR, was used to incubate with lipoproteins for further examination. The results elucidated that the uptake of triglyceride rich lipoprotein mediated by VLDLR plays an important role in accumulation of lipid and the formation of foam cells.

Exploration of the Relationship between Phlegm-Dampness Constitution and Polymorphism of Low Density Lipoprotein Receptor Genes Pvu Ⅱand AvaⅡ

Objective： To explore the polymorphism of low density lipoprotein receptor （LDL-R） genes Pvu Ⅱ end Ave Ⅱ in e population with phlegm-dampness constitution （PDC）. Methods： Polymorphism of LDL-R genes at Pvu Ⅱ end Ave Ⅱ of 48 persons with gentle constitution （GC） end 61 with PDC were analyzed with PCR-RELP technique, end their serum contents of lipids end glucose were determined end compared as well. Results： The A＋ ellelic end P- ellelic frequency were higher end the P＋ ellelic frequency was lower in subjects with PDC then those in subjects with GC, which were 0.3083 vs 0.1771, 0.9098 vs 0.7708 end 0.0902 vs 0.2292, respectively, ell showing significant difference between the two groups （P〈0.05）. Comparison of the two groups in serum levels of triglyceride （TG）, fasting blood glucose, 2 h postprandial blood glucose, end 2 h postprandial insulin showed that ell the parameters were higher in subjects with PDC then in subjects with GC respectively, showing significant difference （P〈0.05）. Conclusion： PDC is related with the P- end A＋ ellelic frequency of higher LDL-R genes at Pvu Ⅱ end Ave Ⅱ, therefore, the polymorphism of LDL-R genes could be taken as one of the genetic markers for PDC, end humans with PDC ere more liable to suffer from blood lipids end glucose disorder then those with GC.

Effect of Insulin on the Differential Expression of VLDL Receptor Isoforms of SGC7901 Cell and Its Biological Implication

This study examined the effect of insulin on the expression of very low density lipoprotein receptor (VLDLR) subtypes of SGC7901 cells and discussed its biological implication.In vitro, moderately or poorly-differentiated human gastric adenocarcinoma cell line SGC7901 was incubated with insulin for different lengths of time, and then the expression of protein and RNA level in VLDLR subtypes were detected by Western blotting and real-time PCR, respectively.The results showed that, at certain time interval, insulin could down-regulate expression of type Ⅰ VLDLR and up-regulate the expression of type Ⅱ VLDLR in SGC7901 cells, at both protein and RNA level.We are led to conclude that insulin serves as a regulator in maintaining the balance between glucose and lipid metabolism in vivo, possibly through its effect on the differential expression of VLDLR subtypes.

Mitofusin2 Decreases Intracellular Cholesterol of Oxidized LDL-Induced Foam Cells from Rat Vascular Smooth Muscle Cells

Mitofusin2 （Mfn2） plays a pivotal role in the proliferation and apoptosis of vascular smooth muscle cells （VSMCs）. The purpose of this study was to investigate the effects of Mfn2 on the traffick- ing of intracellular cholesterol in the foam ceils derived from rat VSMCs （rVSMCs） and also to investigate the effects of Mfn2 on the expression of adenosine triphosphate-binding cassette subfamily A member 1 （ABCA1）, adenosine triphosphate-binding cassette subfamily G member 1 （ABCG1） and peroxisome proliferator-activated receptor gamma （PPARy）. The rVSMCs were co-cultured with oxi- dized low density lipoprotein （LDL, 80 ~tg/mL） to produce foam cells and cholesterol accumulation in cells. Before oxidized LDL treatment, different titers （20, 40 and 60 pfu/cell） of recombinant adenovirus containing Mfn2 gene （Adv-Mfn2） were added into the culture medium for 24 h to transfect the Mfn2 gene into the rVSMCs. Then the cells were harvested for analyses. The protein expression of Mfn2 was significantly higher in Adv-Mfn2-transfected group than in untransfected group （P〈0.05）, and the ex- pression levels significantly increased when the titer of Adv-Mfn2 increased （P〈0.05）. At 24 or 48 h af- ter oxidized LDL treatment, rVSMCs became irregular and their nuclei became larger, and their plasma abounded with red lipid droplets. However, the number of red lipid droplets was significantly decreased in Adv-Mfn2-transfected group as compared with untransfected group. At 48 h after oxidized LDL treatment, the intracellular cholesterol in rVSMCs was significantly increased （P〈0.05）, but it was sig- nificantly decreased in Adv-Mfn2-transfected group as compared with untransfected group （P〈0.05）, and it also significantly decreased when the titer of Adv-Mfn2 increased （P〈0.05）. The mRNA and pro- tein expression levels of ABCA1 and ABCG1 were significantly increased in Adv-Mfn2-transfected group as compared with untransfected group （P〈0.05）. Though the mRNA and protein expression levels of PPARy was not significantly increased （P〉0.05）, the phosporylation levels of PPARy were signifi- cantly decreased in Adv-Mfn2-transfected group as compared with untransfected group （P〈0.05）. These results suggest that the transfection of Adv-Mfn2 can significantly reduce intracellular cholesterol in oxidized LDL-induced rVSMCs possibly by decreasing PPAR＇/phosporylation and then increasing pro- tein expression levels of ABCAI and ABCG1, which may be helpful to suppress the formation of foam cells.

Cholesterol metabolism in cholestatic liver disease and liver transplantation:From molecular mechanisms to clinical implications

The aim of this review is to enlighten the critical roles that the liver plays in cholesterol metabolism. Liver transplantation can serve as gene therapy or a source of gene transmission in certain conditions that affect cholesterol metabolism, such as low-density-lipoprotein(LDL) receptor gene mutations that are associated with familial hypercholesterolemia. On the other hand, cholestatic liver disease often alters cholesterol metabolism. Cholestasis can lead to formation of lipoprotein X(Lp-X), which is frequently mistaken for LDL on routine clinical tests. In contrast to LDL, Lp-X is non-atherogenic, and failure to differentiate between the two can interfere with cardiovascular risk assessment, potentially leading to prescription of futile lipid-lowering therapy. Statins do not effectively lower Lp-X levels, and cholestasis may lead to accumulation of toxic levels of statins. Moreover, severe cholestasis results in poor micellar formation, which reduces cholesterol absorption, potentially impairing the cholesterol-lowering effect of ezetimibe. Apolipoprotein B-100 measurement can help distinguish between atherogenic and non-atherogenic hypercholesterolemia. Furthermore, routine serum cholesterol measurements alone cannot reflect cholesterol absorption and synthesis. Measurements of serum non-cholesterol sterol biomarkers- such as cholesterol precursor sterols, plant sterols, and cholestanol- may help with the comprehensive assessment of cholesterol metabolism. An adequate cholesterol supply is essential for liver-regenerative capacity. Low preoperative and perioperative serum cholesterol levels seem to predict mortality in liver cirrhosis and after liver transplantation. Thus, accurate lipid profile evaluation is highly important in liver disease and after liver transplantation.

Peroxisome proliferator-activated receptor a agonist attenuates oxidized-low density lipoprotein induced immune maturation of human monocyte-derived dendritic cells

Accumulating evidence suggests that the Thl immune .response induced by various antigens such as oxidized low density lipoprotein （ox-LDL） and heat shock proteins （HSPs） play a key role in the process of atherosclerosis.1Dendritic cells （DCs） are the most potent antigen-presenting cells （APCs） in the body with the unique ability to initiate a primary immune response to certain antigens by the activation of ＂naive＂ T cells.2 The maturation of DC with the upregulation of costimulatory molecules such as CD83, CD40, CD86, and major histocompatibility complex （MHC） class molecules such as human leukocyte antigen （HLA）-DR, is required for DC to activate T cells. Pathologic studies have shown that immature DCs are present in normal arterial while abundant mature DCs clustered with T cells could be visualized in atherogenic vessels suggesting that DC 3 maturation is linked to the progression of atherosclerosls. Peroxisome proliferator-activated receptors （PPARs） a, one member of the family of PPARs, was found to have favorable effects on slowing the progression of atherosclerosis and reducing the risk of coronary heart disease in high-risk patients independent from their metabolism effects.4＇5 Furthermore, PPAR-α is also expressed on monocytes and monocyte-derived DCs.6 The effects of PPAR-α on DCs maturation and immune function remain unknown now, we therefore observed the effects of fenofibrate, a PPAR-α agonist, on the maturation and immune function of oxidized LDL-treated DCs in this study.