BACKGROUND/AIMS: Changes in lipid profiles in patients infected with hepatitis C virus (HCV) during direct-acting antiviral therapy have been reported in recent years. However, the clinical aspects of disturbed lipid metabolism in chronic HCV infection have not been fully elucidated. METHODS: Dynamic changes in serum total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol and apolipoprotein levels in patients infected with HCV genotype 1b were examined during combination therapy with daclatasvir (DCV) and asunaprevir (ASV). RESULTS: Total, LDL−, and HDL-cholesterol levels increased rapidly and persistently after week 4. Apolipoprotein (apo) A-I, apo B, apo C-II, and apo C-III levels were significantly higher at week 4 than at week 0. In contrast, apo A-II and apo E levels were significantly lower. The differences in LDL− and HDL-cholesterol levels were positively correlated with those of apo B and apo A-I, respectively. Interestingly, in patients with non-sustained virological response, these cholesterol levels decreased rapidly after viral breakthrough or viral relapse. Furthermore, similar changes were observed for apo A-I, apo B and apo C-III levels. CONCLUSIONS: Clearance of HCV using combination therapy with DCV and ASV results in rapid changes in serum lipid profiles, suggesting an influence of HCV infection on disturbed lipid metabolism.
Apolipoprotein A-I ; Apolipoprotein A-II ; Apolipoprotein C-II ; Apolipoprotein C-III ; Apolipoproteins ; Apolipoproteins B ; Apolipoproteins E ; Cholesterol ; Genotype ; Hepacivirus* ; Hepatitis C* ; Hepatitis* ; Humans ; Lipid Metabolism ; Lipoproteins ; Recurrence

PURPOSE: Apolipoprotein E (Apo E) plays a major role in lipoprotein metabolism and lipid transport. Many investigators have described that Apo E polymorphisms is one of the most important genetic determinants for cardiovascular disease. The purpose of this study was to evaluate the association between Apo E polymorphisms and serum lipid profiles in obese adolescent. METHODS: We measured the serum concentrations of glucose, apolipoprotein (Apo) A1, Apo B, total cholesterol (TC), triglyceride (TG), HDL and LDL-cholesterol after overnight fasting in obese adolescent. Apo E polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: 86 obese adolescents participated in this study. The body mass index (BMI) of participants were excess of 95 percentile by age and sex. Male to female ratio was 1.7 and mean age of study group was 16.2+/-1.8 years. Mean BMI was 27.4+/-2.5 kg/m2. The frequency of epsilon2, epsilon3 and epsilon4 allele were 8.1%, 87.2% and 4.7% respectively. Study populations were classified into the following three genotypes 1) Apo E2 group (n=13, 15.1%) carrying either the epsilon2/epsilon2 or epsilon2/epsilon3 2) Apo E3 group (n=65, 75.6%) carrying the most frequent epsilon3/epsilon3 3) Apo E4 group (n=8, 9.3%) carrying either the epsilon3/epsilon4 or epsilon4/epsilon4. No differences were found among Apo E genotypes concerning age, sex, weight, height and BMI. Apo B and LDL-cholesterol concentrations were significantly higher in the Apo E4 group (P<0.05). No association were found between Apo E genotypes and glucose, Apo A1, TC, TG and HDL. CONCLUSIONS: We confirmed that serum concentrations Apo B and LDL-cholesterol were influenced by Apo E genotypes. Apo E polymorphisms seems to influence some alteration of lipid metabolism associated with obesity in adolescent.
Adolescent ; Alleles ; Apolipoprotein A-I ; Apolipoprotein E2 ; Apolipoprotein E3 ; Apolipoprotein E4 ; Apolipoproteins ; Apolipoproteins B ; Apolipoproteins E ; Body Mass Index ; Cardiovascular Diseases ; Cholesterol ; Fasting ; Female ; Genotype ; Glucose ; Humans ; Lifting ; Lipid Metabolism ; Lipoproteins ; Male ; Obesity ; Research Personnel

Human apolipoprotein A- I, the major protein component of high density lipoproteins and the main activator of the enzyme lecithin: cholesterol acyltransferase, defines the structure and stability and functions of HDL. It is clearly demonstrated that high concentration of the apoA- I not only inhibits the initiation and progression of atherosclerosis, but also makes the preexisting atherosclerotic lesions regress. This review gives an overview of the apoA- I structure, production, relation between apoA- I and HDL, and several mechanisms of the apoA-I anti-atherosclerosis. These mechanisms include directing excess celluar cholesterol from the peripheral tissues to the liver in reverse cholesterol transport, inhibiting oxidative modification of LDL, and modulating inflammatory responses to favour vasoprotection.
Animals ; Apolipoprotein A-I ; chemistry ; metabolism ; physiology ; Atherosclerosis ; metabolism ; prevention & control ; Cholesterol ; metabolism ; Humans ; Lipoproteins, HDL ; metabolism ; physiology

This study was aimed to observe if the lipid profiles, apoprotein B100 (ApoB100), ApoAI, high density lipoprotein (HDL) and its subclasses could be improved by controlling the blood glucose. Fifty-three patients with newly diagnosed type 2 diabetic were divided into four groups, diet and exercise group (n = 13), continuous subcutaneous insulin infusion (CSII) group (n = 14), multiple daily insulin injection group (MDI, n = 13), and oral hypoglycaemic agents group (n = 13). Fasting blood glucose (FPG), glycated hemoglobin A1c (HbA1c), lipid profiles, ApoB100, ApoAI and HDL subclasses were measured at beginning and a month later. Forty-three patients finished the testing. The levels of FPG, HbA1c, triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and ApoB100 were decreased significantly (P < 0.05) in all groups, and ApoAI/ApoB100 increased obviously (P < 0.05). Comparatively matured HDL subclasses such as HDL2b were increased (P < 0.05), and comparatively infantile HDL subclasses such as HDL3b were decreased (P < 0.05). Therapy with hyperglycemic agents improved TG, TC, LDL-C, ApoB100, ApoAI/ApoB100, and HDL2b significantly (P < 0.05), but intervention with the diet and exercise group alone did not improve lipid profiles, apolipoproteins, and HDL subclasses (P > 0.05). Meanwhile, therapy with insulin intensive therapy (MDI, CSII) group had the most powerful effect on decreasing ApoB100 concentration (P < 0.05). The results suggested that lipid profiles, apolipoproteins, and quantity and quality of HDL subclasses might be improved by blood glucose controlling.
Adult ; Aged ; Apolipoprotein A-I ; blood ; Apolipoprotein B-100 ; blood ; Blood Glucose ; metabolism ; Cholesterol, HDL ; blood ; classification ; Diabetes Mellitus, Type 2 ; blood ; Female ; Humans ; Lipids ; blood ; Male ; Middle Aged

Apolipoprotein A-I-Milano(AIM), a natural variant, not only inhibits the initiation and progression of atherosclerosis, but also makes the preexisting atherosclerotic lesions regress. AIM gene, at which N-terminal codens were optimized, was subcloned into the expression vector of pET22b. Recombiant plasmids were transformed into E. coli strain BL21 (DE3) and induced with IPTG. The expressed apoliprotein A-I-Milano was soluble in E. coli and was about 38% of total cell lysate. Purified by Butyl Sepharose 4F. F hydrophobic chromatography and Q Sepharose H.P. anion exchange chromatography, followed by ultrafiltration with Vivaspin 20 (30 000MW), AIM monomer was obtained in a purity of more than 95%. Activity assay of binding of AIM monomer to lipid indicates that association of AIM monomer with DMPC is slower than normal apoA-I but DMPC number associated by AIM monomer is more than by apoA-I. This results will be important for studying structure, function of AIM, specially clinical application.
Apolipoprotein A-I ; biosynthesis ; genetics ; Escherichia coli ; genetics ; metabolism ; Humans ; Mutant Proteins ; biosynthesis ; genetics ; Recombinant Proteins ; biosynthesis ; genetics ; Solubility

OBJECTIVETo investigate the effects of a high-carbohydrate diet on the lipid and apolipoprotein ratios in healthy young adults with different genotypes of the polymorphism at -75 site in the promoter region of the gene of apolipoprotein AI (APOA1).

METHODSFifty-six subjects aged (22.89 +/- 1.80) years were given a wash-out diet for 7 days, followed by a high-carbohydrate diet for 6 days. The wash-out diet contained 15% protein, 31% fat, and 54% carbohydrate. The high-carbohydrate diet contained 15% protein, 15% fat, and 70% carbohydrate. Twelve-hour fasting serum lipids and apolipoproteins B100 and AI were measured on the mornings of the 1st, the 8th, and the 14th days from the beginning of the wash-out diet. The ratios of triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC)/HDL-C, low-density lipoprotein cholesterol (LDL-C)/HDL-C, and apolipoprotein B100 (APOB100)/apolipoprotein AI (APOAI) were calculated. The genome DNA was extracted and the polymorphism of APOA1 -75 G/A was determined by polymerase chain reaction followed by restriction fragment length polymorphism assay.

RESULTSAt baseline, the lipid and apolipoprotein ratios showed no significant differences between the GG genotype and the A carriers in males (P > 0.05), whereas the female A carriers had a significantly higher ratio of LDL-C/ HDL-C compared with the female subjects with the GG genotype (P < 0.05). Following the high-carbohydrate diet, significant decreases of TC/HDL-C were found in all the groups, regardless of sex and genotype (P < 0.01). LDL-C/HDL-C experienced significant decreases in both the genotypes in males (P < 0.05), while in females, significant decrease of LDL-C/HDL-C was only observed in A carriers (P < 0.01).

CONCLUSIONThe A allele of the -75 G/A polymorphism in APOA1 may have specific effects on the LDL-C/HDL-C ratio in females.

Adult ; Apolipoprotein A-I ; genetics ; Apolipoproteins ; blood ; Dietary Carbohydrates ; metabolism ; Female ; Genotype ; Humans ; Lipids ; blood ; Male ; Polymorphism, Genetic ; Young Adult

The work was aimed to investigate the differential expressions of lipid metabolism related genes in the early stage of atherosclerosis in the young apolipoprotein E deficient (apoE(-/-)) mice at different ages with normal chow diet. The genotypes of mice were identified by using multiplex polymerase chain reaction (multi-PCR) analysis. The semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and real-time quantitative RT-PCR were used to analyze the expressions of lipid metabolism related genes in the liver of apoE(-/-) and age-matched wild type (WT) mice of 14-day old, 1-month old, 2-month old, 3-month old. The serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) contents were assayed using COD-PAP and GPO-PAP methods. The serum apolipoprotein B100 (apoB100) content was quantitated by immune turbidimetry. The hearts were perfusion-fixed in 4% formaldehyde, infiltrated with 30% gum sucrose for 24 h at 4 °C, and embedded in OCT compound. The aortic sinus tissues were serially sectioned at -15 °C, stained with Sudan IV, and counterstained with light green. The results were shown as follows. Compared with that in WT mice, the mRNA levels of apoA I and apoA IV in apoE(-/-) mice aged from 14-day old to 3-month old changed prominently (P<0.05), with apoA I up-regulated and apoA IV down-regulated. At the age of 1 month, the expression of apoB100 in apoE(-/-) mice was higher than that in WT mice (P<0.05). The expression of apoA V was up-regulated (P<0.05) and there was obvious lipid deposition in the aortic intima in apoE(-/-) mice at the age of 2 months. The expressions of fatty acid translocase (Fat/CD36) and angiopoietin-like protein 3 (Angptl 3) in apoE(-/-) mice were higher than those in WT mice at the age of 3 months (P<0.05), while the expressions of peroxisome proliferator-activated receptor α (PPARα), liver X receptor α (LXRα), carnitine palmitoyl transferase I (CPT I) and acyl coenzyme A oxidase 1 (ACOX1) showed no significant changes. The serum TC, TG, LDL-C and HDL-C contents in apoE(-/-) mice aged from 14-day old to 3-month old were higher than those in age-matched WT mice. apoE(-/-) mice showed a marked increase in serum apoB100 content, consistent with the trend of serum LDL-C content and apoB100 mRNA content in the liver. The results suggest that the mRNA expressions of apoA I, apoA IV, apoA V, apoB100 and Angptl 3 in apoE(-/-) mice change significantly compared with those in WT mice, and these genes might be relevant to the complicated lipid metabolism network, and involved in the early stage of atherogenesis.
Animals ; Apolipoprotein A-I ; metabolism ; Apolipoprotein B-100 ; blood ; Apolipoproteins A ; metabolism ; Apolipoproteins E ; genetics ; Atherosclerosis ; genetics ; Gene Expression ; Lipid Metabolism ; genetics ; Lipoproteins, HDL ; blood ; Lipoproteins, LDL ; blood ; Liver ; metabolism ; Mice ; Mice, Knockout ; Triglycerides ; blood

Apolipoprotein A- I is the major apolipoprotein in high-density lipoprotein known to have a wide range of physiological functions, the best-studied one of which is in regulating cholesterol metabolism and preventing arteriosclerosis. Human blood has been the only source of this protein. To facilitate further research and application, it is essential to produce it through genetic engineering. In the current research, the baculovirus-insect cell system was used to overexpress human apolipoprotein A- I . Two recombinant baculoviruses were constructed. The first one expressed a pro form of apoA- I lacking native signal peptide. The recombinant protein was found to remain mainly inside cells in the early phase of infection, while being largely excreted to the medium late in infection. The second one used a heterologous signal peptide, snake phospholipase A2 inhibitor alpha subunit signal peptide, to lead the secretion of mature apoA- I. In contrast to the first virus, recombinant apoA- I was found in the culture medium at the early phase of virus infection. The mature apoA- I was purified from culture medium using Phenyl Sepharose hydrophobic interaction chromatography (HIC) and eluted with water and Propylene. This work shows that snake phospholipase A2 inhibitor a subunit signal peptide can be used to secret human apoA- I in insect cells, but the efficiency of its secretion is limited when the expression level is high.
Animals ; Apolipoprotein A-I ; genetics ; metabolism ; Baculoviridae ; genetics ; Blood Proteins ; genetics ; metabolism ; Blotting, Western ; Cell Line ; Chromatography ; Genetic Vectors ; genetics ; Humans ; Recombinant Proteins ; genetics ; metabolism ; Snakes ; Spodoptera ; cytology

Effect of antiatherogenic high density lipoprotein (HDL) and apolipoprotein AI (apoAI) on production of prostaglandin E2 (PGE2) by human monocyte-derived macrophages was investigated. Macrophages were loaded with acetylated low density lipoprotein followed by incubation with HDL3 or apoAI. PGE2 produced and secreted in culture supernatant was quantified by enzyme immunoassay. HDL3 induced production of PGE2 by macrophages in a time-dependent manner. 24 h after incubation, PGE2 production by HDL3-treated macrophages increased 3.7-fold of that by control cells. ApoAI also induced PGE2 secretion to 2.1-fold, which was significantly less than HDL3. The data indicate that both HDL3 and lipid-free apoAI enhance PGE2 synthesis and secretion by human macrophages and this may further contribute to the protection from atherosclerosis.
Apolipoprotein A-I ; pharmacology ; Arteriosclerosis ; prevention & control ; Culture Media, Conditioned ; Dinoprostone ; biosynthesis ; Humans ; Lipoproteins, HDL ; pharmacology ; Lipoproteins, HDL3 ; Macrophages ; cytology ; metabolism ; Monocytes ; metabolism

OBJECTIVE: To explore the clinical value of virtual touch tissue quantification (VTQ) technique and the PGA index [prothrombin time (P), γ-glutamyl transpeptadase (GG) and apolipoprotein A1 (ApoAl)] in evaluating the degree of liver fibrosis in alcoholic patients.
 METHODS: A total of 64 patients with long-term alcohol history were enrolled for this study. The liver ultrasonography elasticity was examined by VTQ techniques, the VTQ value was assessed in the liver target region, and then the PGA index was calculated. According the liver biopsy biological results, a golden standard, the patients were divided into a non-fibrosis group (n=11), a fibrosis group (n=10), a significant fibrosis group (n=14) and a cirrhosis group (n=29). The diagnostic value of VTQ and PGA index were compared in alcoholic patients following the classification of liver fibrosis.
 RESULTS: The elastography VTQ values were (1.38±0.33), (1.49±0.30), (1.76±0.22) and (2.28±0.53) m/s; while the PGA indexes were 2.09±0.94, 2.30±1.06, 3.57±1.09, and 2.21±1.99 in the non-fibrosis group, the fibrosis group, the significant fibrosis group and the cirrhosis group, respectively. The VTQ value and PGA index were positively correlated with the classification of liver fibrosis (VTG: r=0.719, PGA: r=0.683; both P<0.01).
 CONCLUSION The alcoholic liver fibrosis can be assessed by noninvasive VTQ technology and PGA index. As a real-time ultrasound elastography technique, VTQ is more accurate than the PGA index. Combination of the two methods is helpful for early diagnosis and treatment in the patients with alcoholic liver fibrosis.
Apolipoprotein A-I ; metabolism ; Biopsy ; Elasticity Imaging Techniques ; Humans ; Liver Cirrhosis, Alcoholic ; classification ; diagnostic imaging ; Predictive Value of Tests ; Prothrombin Time ; Reproducibility of Results ; gamma-Glutamyltransferase ; metabolism