Serum Apo Research Articles

Identification of serum APOA1 and APOC3 as potential biomarkers of aplastic anemia

Identification of serum APOA1 and APOC3 as potential biomarkers of aplastic anemia

The associations between apolipoprotein B, A1, and the B/A1 ratio and nonalcoholic fatty liver disease in both normal-weight and overweight Korean population

Nonalcoholic fatty liver disease (NAFLD) is associated with a higher risk of cardiovascular disease, but the relationship has not been established in nonobese populations. Higher apolipoprotein B (apo B) levels and the apo B/A1 ratio and lower apo A1 levels are associated with an elevated risk of cardiovascular disease. We investigated the associations between apo B, apo A1, and the apo B/A1 ratio and the presence of metabolic syndrome and NAFLD in both normal-weight and overweight Koreans. This cross-sectional study consisted of 8327 consecutive both normal-weight and overweight Koreans with NAFLD diagnosed by ultrasonography at the Samsung Medical Center in Korea from January 2008 to December 2010. The prevalence of NAFLD was 27.1% among the 8327 participants. Higher serum triglyceride levels and the apo B/A1 ratio and lower high-density lipoprotein cholesterol and apo A1 levels were significantly associated with higher prevalence of metabolic syndrome in both normal-weight group and overweight group. The multivariate-adjusted odds ratios (ORs) for NAFLD in normal-weight group after comparing the fourth vs the first quartiles of the triglyceride, HDL cholesterol, low-density lipoprotein (LDL) cholesterol, apo B, apo A1, and the apo B/A1 ratio data were 2.89 (95% confidence interval [CI], 2.19-3.83; P trend < .001), 0.60 (95% CI, 0.46-0.78; P trend < .001), 1.67 (95% CI, 1.33-2.11; P trend < .001), 1.88 (95% CI, 1.48-2.39; P trend < .001), 0.73 (95% CI, 0.58-0.93; P trend < .001), and 1.86 (95% CI, 1.45-2.38; P trend < .001), respectively. The corresponding adjusted ORs in the overweight group were 3.43 (95% CI, 2.60-4.54; P trend < .001), 0.89 (95% CI, 0.68-1.16; P trend = .221), 1.41 (95% CI, 1.11-1.78; P trend = .001), 1.58 (95% CI, 1.21-2.06; P trend < .001), 0.99 (95% CI, 0.77-1.27; P trend = .958), and 1.53 (1.16-2.01; P trend = .002), respectively. Higher serum triglyceride, LDL cholesterol, apo B1 levels, and the apo B/A1 ratio were significantly associated with NAFLD independent of metabolic syndrome in both normal-weight and overweight Koreans. Lower serum HDL cholesterol and apo A1 levels were related to NAFLD in normal-weight participants. Our results suggest that the presence of NAFLD may be associated with increased risk for coronary artery disease in both normal-weight and overweight Koreans.

Is plasma-soluble CD36 associated with density of atheromatous plaque and ankle–brachial index in early-onset coronary artery disease patients?

CD36 is a major macrophage scavenger receptor for oxidised low-density lipoprotein particles. Soluble CD36 (sCD36) is circulating as a ligand-bound complex and may be present in microparticles shed from cells such as platelets, monocytes/macrophages, or adipocytes. Positive association of plasma sCD36 with insulin resistance has been reported, and it has been proposed that sCD36 might represent a marker of macrophage activation and inflammation leading to atherosclerosis. Recently we have identified an association between CD36 polymorphism and low thickness of atheromatous plaque, suggesting its protective effect against atherosclerosis development. To obtain insight into the relationship between plasma concentration of sCD36 and radiological parameters of atherosclerosis in patients with early-onset coronary artery disease (CAD). The study group comprised 70 clinically stable patients (18 women and 52 men) with early CAD (aged no more than 50 years for men and 55 years for women). Fasting blood sample was taken for serum glucose, lipid profile, ApoA1, ApoB, Lp(a), and plasma sCD36 protein measurements. Each subject's weight, height, waist and hip circumference, and systolic and diastolic blood pressure were measured, and the body mass index, waist-to-hip ratio, and mean arterial pressure were calculated. Doppler ultrasound examinations of carotid and peripheral arteries were performed in all patients. Thickness of intima-media complex (IMC) of common carotid (CCA) and brachial arteries, as well as density and thickness of atheromatous plaque at CCA bifurcation, were measured with M'Ath programme. Plasma concentrations of CD36 antigen were measured by ELISA. Correlations between quantitative variables and sCD36 plasma concentration were assessed with the Spearman rank correlation coefficient (Rs). Associations between qualitative variables and sCD36 plasma concentration were tested with the Mann-Whitney U test. We observed no significant correlations between sCD36 concentration and radiological parameters of atherosclerosis. We found only borderline significant negative correlation of sCD36 concentration with thickness of IMC of left brachial artery. We also observed a significantly negative correlation with CCA plaque density, but only in the female subgroup and on the right side. Borderline higher sCD36 plasma concentrations were observed in patients with lower ankle-brachial index value (< 0.9). The results of the study show no strong associations and do not prove either detrimental or beneficial influence of sCD36 on radiological parameters of atherosclerosis. Further research is necessary to assess the association of high plasma sCD36 concentrations with the risk of plaque instability in patients with early-onset CAD.

Abstract 19224: Fibrinogen And Neopterin Predict Future Myocardial Infarction Events In Patients With Stable Coronary Heart Disease

Background: Fibrinogen is synthesized by hepatocytes. It is a precursor of fibrin and forms bridges between platelets during thrombus formation, but it is also a marker of ongoing inflammation. Neopterin is released by monocyte/ macrophage activation associated with atherosclerosis. Whether these markers interact or act independently among patients with suspected stable coronary heart disease has previously not been given much attention. Methods: We included 3526 patients undergoing elective coronary angiography at two university hospitals in Norway during 2000-2004, with a median follow-up of 7.3 years. Cox regression analysis was used to obtain hazard ratios (HR) and 95% confidence intervals (CI) for incident AMI of fibrinogen and neopterin levels in a crude model and a model adjusted for age, gender, diabetes, current smoking, hypertension and serum apoA1 and apoB. Potential effect modifications were investigated according to strata of fibrinogen or neopterin below or above the median, as well as across subgroups of age, gender, smoking status, diabetes, serum apoA1 and apoB. A p-value &lt;0.05 was considered significant. Results: During follow-up, 580 patients experienced an AMI. In the unadjusted model, both fibrinogen and neopterin predicted future AMI [HR = 1.32; 95% CI 1.22-1.43; p&lt;0.001 and HR = 1.31; 95% CI 1.23-1.40; p&lt;0.001, respectively]. The estimates were only slightly attenuated in the multivariate model, and still associated with incident AMI when both biomarkers were added simultaneously [HR = 1.15; 95% CI 1.05-1.25; p&lt;0.001 and HR = 1.20; 95% CI 1.12-1.28; p&lt;0.001, respectively]. Baseline fibrinogen and neopterin levels were modestly correlated (Spearman’s rho = 0.18, p-value &lt;0.001). There were no statistically significant interaction across subgroups (p for interaction fibrinogen and high/ low neopterin = 0.26, neopterin and high/low fibrinogen = 0.46, respectively). Conclusion: Patients with increased levels of fibrinogen or neopterin are at increased risk of future AMI. Neopterin levels did not significantly interact with the prognostic utility of fibrinogen. This suggests that circulating fibrinogen and neopterin may reflect different pathophysiological mechanisms.

Single nucleotide polymorphisms of APOA1 gene and their relationship with serum apolipoprotein A-I concentrations in the native population of Assam

BackgroundThere is a growing interest in the role of allelic variants of the APOA1 gene in relation to a number of disorders. We described two common polymorphisms of the APOA1 gene, G-75A and C+83T and investigated their potential influence on the serum apolipoprotein A-I (apo A-I) levels in the native population of Assam — a region that is ethnically distinct and from where no information is hitherto available. MethodsBlood samples were collected from 150 healthy volunteers. Apo A-I levels were estimated by immunoturbidometry. Genotyping was done by a PCR-RFLP method that involved DNA extraction from whole blood, followed by polymerase chain reaction and digestion of the PCR product by MspI restriction enzyme, and analysis of fragment sizes in 12% polyacrylamide gel. ResultsThe GG variant at G-75A locus and CC variant at C+83T locus were the most prevalent. GG/CC was the most common combination. Homozygous TT genotype was not detected in any of the subjects. The rare allele frequencies for the G-75A and C+83T sites were found to be 0.22 and 0.06 respectively, which significantly differed from those reported in some other populations in neighbouring regions. Serum apo A-I concentrations did not vary significantly across the detected genotypes. These findings were consistent in both sexes. ConclusionWe described the distribution of the G-75A and C+83T polymorphisms of the APOA1 gene in the population of Assam for the first time. These polymorphisms were not found to directly influence apo A-I concentrations in this population either individually or synergistically.

Analysis of -3826A/G polymorphism in the promoter of the uncoupling protein-1 gene in Chinese non-obese and obese populations

To investigate the -3826A/G polymorphism in the promoter of the uncoupling protein-1 (UCP1) gene and its relations to obesity in Chinese population. Three hundred and eighty-four subjects (257 non-obese and 127 obese individuals) from a population of Chinese Han nationality in Chengdu area were studied using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLPs). Serum lipids were measured by enzymatic kits and apolipoproteins A I, A II, B100, C II, C III and E were measured by the RID kits. The frequencies of A and G alleles at -3826A/G site in obese and non-obese groups were 0.508 and 0.492, and 0.467 and 0.533, respectively. It showed no significant difference in allele frequencies between non-obese and obese groups (P > 0.05). In the obese group, subjects with genotype GG had higher serum apo B100 concentrations, and those with genotype AG had higher apo C II and apo C III levels, than those with genotype AA, respectively (P < 0.05). In non-obese male subgroup, subjects with genotype GG had lower serum HDL-C and apo A I levels than those with genotype AA, respectively (P < 0.05), whereas those with genotype AG had lower apo A II levels than those with genotype AA. In addition, in obese males with genotype GG had elevated apo B100 levels compared with those with genotype AA, whereas in obese females with genotype GG had decreased apo AI levels and genotype AG had increased apo C II and apo C III levels compared with those with genotype AG and AA, respectively (P < 0.05). -3826A/G polymorphism in the promoter of the uncoupling protein-1 gene was not associated with obesity in Chinese Han population of Chengdu area. It may be associated with serum HDL-C, apo A I and apo B100 levels in non-obese and/or obese subjects of certain genders.

Protective associations of HDL with blood-brain barrier injury in multiple sclerosis patients

The purpose of this work was to investigate the associations of serum cholesterol and apolipoproteins with measures of blood-brain barrier (BBB) permeability and CNS inflammation following the first clinical demyelinating event. This study included 154 patients [67% female; age, 29.5 ± 8.2 years (mean ± SD)] enrolled in a multi-center study of interferon β1-a treatment following the first demyelinating event. Blood and cerebrospinal fluid (CSF) were obtained at screening prior to treatment. A comprehensive serum lipid profile and multiple surrogate markers of BBB breakdown and CNS immune activity were obtained. Higher levels of serum HDL cholesterol (HDL-C) and ApoA-I were associated with lower CSF total protein level, CSF albumin level, albumin quotient, and CSF IgG level (all P ≤ 0.001 for HDL-C and all P < 0.01 for ApoA-I). HDL-C was also associated with CSF CD80+ (P < 0.001) and with CSF CD80+CD19+ (P = 0.007) cell frequencies. Higher serum HDL is associated with lower levels of BBB injury and decreased CD80+ and CD80+CD19+ cell extravasation into the CSF. HDL may potentially inhibit the initiation and/or maintenance of pathogenic BBB injury following the first demyelinating event.

Association of systemic inflammation with the serum apolipoprotein A-1 level: A cross-sectional pilot study

BackgroundThere is growing evidence to suggest that measurement of apolipoprotein A-1 (apoA-1), the main surface protein on high-density lipoprotein (HDL) particles, is superior to measurement of the serum HDL-cholesterol level as a predictor of the occurrence of coronary disease (CAD). We investigated the association of systemic inflammation as an initiator of CAD along with the serum apoA-1 level. Methods and resultsThis study was designed as a hospital-based cross-sectional study on 652 consecutive outpatients with at least one risk factor for CAD to investigate the relationships between the serum high-sensitivity C-reactive protein (hs-CRP) and the peripheral blood white blood cell (WBC) count and the serum apoA-1 level between April 2009 and October 2009. Multivariate analysis after adjustments for traditional coronary risk factors revealed reduced apoA-1 as an independent indicator of higher hs-CRP and WBC count, both in the overall subject population (β: −0.270 and −0.116, p<0.0001 and 0.003) and in a patient subset with serum low-density lipoprotein cholesterol <100mg/dL (β: −0.280 and −0.128, p<0.0001 and 0.045). However, in the patients who could be followed up 6 months later, the increase in the apoA-1 level was associated with a decrease in the hs-CRP level, but not with a decrease in the WBC count. ConclusionsIncreased serum apoA-1 levels may be associated with decreased hs-CRP levels and decreased WBC counts as predictive inflammatory biomarkers of the onset of CAD. In particular, increase in the hs-CRP level and decrease in the apoA-1 level may be useful indices of the risk of CAD.

Component-Specific Analysis of Plasma Protein Corona Formation on Gold Nanoparticles Using Multiplexed Surface Plasmon Resonance.

At the nano-bio interface, human plasma differentially interacts with engineered nanomaterials through the creation of protein coronas, which in turn become primary determinants of both the pharmacokinetics and pharmacodynamics of circulating nanoparticles. Here, for the first time, the specific binding kinetics of the four major corona forming proteins (human serum albumin, fibrinogen, ApoA1, and polyclonal IgG) are determined for gold nanoparticles (AuNPs). Using a multiplexed surface plasmonic assay, highly reproducible measurements of on rate (k(on)), off rate (k(off)), and disassociation constant (K(D)), in addition to relative amounts of protein binding, are obtained. Dramatic differences in k(on) for individual components are shown as primary determinants of protein affinities, with k(on) ranging over nearly two orders of magnitude for the proteins studied, while k(off) remains within a factor of two for the set. The effect of polyethylene glycol (PEG) modification on plasma component binding is also studied and the effect of PEG length on human serum interaction is characterized through systematic screening of PEG molecular weight (2-30k). The effect of nanoparticle modification on particle targeting is also characterized through study of a hybrid AuNP system.

A novel truncated form of apolipoprotein A-I transported by dense LDL is increased in diabetic patients

Diabetic (DM) patients have exacerbated atherosclerosis and high CVD burden. Changes in lipid metabolism, lipoprotein structure, and dysfunctional HDL are characteristics of diabetes. Our aim was to investigate whether serum ApoA-I, the main protein in HDL, was biochemically modified in DM patients. By using proteomic technologies, we have identified a 26 kDa ApoA-I form in serum. MS analysis revealed this 26 kDa form as a novel truncated variant lacking amino acids 1-38, ApoA-IΔ(1-38). DM patients show a 2-fold increase in ApoA-IΔ(1-38) over nondiabetic individuals. ApoA-IΔ(1-38) is found in LDL, but not in VLDL or HDL, with an increase in LDL3 and LDL4 subfractions. To identify candidate mechanisms of ApoA-I truncation, we investigated potentially involved enzymes by in silico data mining, and tested the most probable molecule in an established animal model of diabetes. We have found increased hepatic cathepsin D activity as one of the potential proteases involved in ApoA-I truncation. Cathepsin D-cleaved ApoA-I exhibited increased LDL binding affinity and decreased antioxidant activity against LDL oxidation. In conclusion, we show for the first time: a) presence of a novel truncated ApoA-I form, ApoA-IΔ(1-38), in human serum; b) ApoA-IΔ(1-38) is transported by LDL; c) ApoA-IΔ(1-38) is increased in dense LDL fractions of DM patients; and d) cathepsin D-ApoA-I truncation may lead to ApoA-IΔ(1-38) binding to LDLs, increasing their susceptibility to oxidation and contributing to the high cardiovascular risk of DM patients.

Natural human apoA-I mutations L141RPisa and L159RFIN alter HDL structure and functionality and promote atherosclerosis development in mice

ObjectiveMutations in human apolipoprotein A-I (apoA-I) are associated with low high-density lipoprotein (HDL) cholesterol levels and pathological conditions such as premature atherosclerosis and amyloidosis. In this study we functionally characterized two natural human apoA-I mutations, L141RPisa and L159RFIN, in vivo. MethodsWe generated transgenic mice expressing either wild-type (WT) or the two mutant forms of human apoA-I on a mouse apoA-I−/− background and analyzed for abnormalities in their lipid and lipoprotein profiles. HDL structure and functionality, as well as atherosclerosis development following a 14-week high-fat diet were assessed in these mice. ResultsThe expression of either apoA-I mutant was associated with markedly reduced serum apoA-I (<10% of WT apoA-I), total and HDL-cholesterol levels (∼20% and ∼7% of WT apoA-I, respectively) and the formation of few small size HDL particles with preβ2 and α3, α4 electrophoretic mobility. HDL particles containing either of the two apoA-I mutants exhibited attenuated anti-oxidative properties as indicated by their inability to prevent low-density lipoprotein oxidation, and by decreased activities of paraoxonase-1 and platelet-activating factor acetylhydrolase. However, the apoA-I(L141R)Pisa or apoA-I(L159R)FIN-containing HDL particles demonstrated increased capacity to promote ATP-Binding Cassette Transporter A1-mediated cholesterol efflux from macrophages. Expression of apoA-I(L141R)Pisa or apoA-I(L159R)FIN mutations in mice was associated with increased diet-induced atherosclerosis compared to either WT apoA-I transgenic or apoA-I−/− mice. ConclusionsThese findings suggest that natural apoA-I mutations L141RPisa and L159RFIN affect the biogenesis and the functionality of HDL in vivo and predispose to diet-induced atherosclerosis in the absence of any other genetic defect.

Association of polymorphisms in the MAFB gene and the risk of coronary artery disease and ischemic stroke: a case-control study.

BackgroundThe v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B gene (MAFB) has been associated with serum lipid levels in the Eurpean population, but little is known about such association in the Chinese population or in atherosclerosis-related patients. Therefore, the purpose of the present study was to assess the association of the single nucleotide polymorphisms (SNPs) in the MAFB and serum lipid levels and the risk of coronary artery disease (CAD) and ischemic stroke (IS) in the Chinese population.MethodsA total of 1,065 unrelated patients (CAD, 525 and IS, 540) and 539 healthy controls were recruited in this study. Genotypes of the MAFB rs2902940 and rs6102059 SNPs were determined by the Snapshot technology platform.ResultsThe rs2902940AA genotype was associated with an increased risk of CAD (adjusted OR = 1.63, 95 % CI = 1.07–2.48, P = 0.023) and IS (adjusted OR = 1.69, 95 % CI = 1.09–2.61, P = 0.017). The rs2902940GA/AA genotypes were also associated with an increased risk of CAD (adjusted OR = 1.56, 95 % CI = 1.04–2.32, P = 0.030 for GA/AA vs. GG) and IS (adjusted OR = 1.72, 95 % CI = 1.14–2.60, P = 0.010 for GA/AA vs. GG). Significant interactions were observed only in those with higher body mass index (BMI), hypertension and diabetes (P < 0.05). The subjects with rs2902940GA/AA genotypes in controls had lower serum ApoAI levels than the subjects with GG genotype (P = 0.024).ConclusionsThe rs2902940A allele carriers in the MAFB conferred a decreased serum ApoAI level in controls and an increased risk of CAD and IS. The rs2902940GA/AA genotypes interacted with higher BMI, hypertension and diabetes to contribute the risk of CAD and IS.

Effect of atorvastatin and niacin/LRPT on apolipoprotein e distribution, metabolism and glycation

Aim: To investigate the influence of apoE genotype on the response to atorvastatin treatment in patients with Type 2 diabetes with nephropathy and the effect of niacin/laropiprant (LRPT) on apoE and glycated apoE concentration and distribution in hyperlipidaemia.Methods: ApoE genotype and the effect of 10mg/day and 80mg/day atorvastatin treatment on apoE concentration were studied in 85 patients with type 2 diabetes with nephropathy. The effect of niacin/LRPT on apoE and glycated apoE was investigated for 36 patients with hyperlipidaemia. Results: After 12 months treatment with atorvastatin, serum apoE concentration decreased significantly in the 80mg/day, but not the 10mg/day group. This decrease was observed in patients with E3 and E4 but not E2 genotype. Hyperlipidaemia did not affect total apoE, but the apoE distribution in HDL and d>1.21g/ml lipoprotein fractions was significantly lower. Glycated apoE was significantly higher in patients with hyperlipidaemia than healthy volunteers (p<0.0001). After 3 months treatment with niacin/LRPT, apoE in apoB?containing lipoproteins (VLDL+LDL) was significantly reduced, but was unchanged in apoA-containing lipoproteins (HDL) compared with treatment with placebo. Niacin/LRPT also had no effect on the elevated glycated apoE observed in patients with hyperlipidaemia.Conclusions: The effect of atorvastatin on total apoE concentration is dependent on the dose of atorvastatin and apoE genotype in patients with type 2 diabetes with nephropathy. Niacin/LRPT has no significant effect on total apoE and glycated apoE, but does influence their distribution in lipoprotein fractions in patients with hyperlipidaemia.

Association of the angiopoietin-like protein 8 rs2278426 polymorphism and several environmental factors with serum lipid levels.

The present study was performed to examine the association of the angiopoietin-like protein 8 (ANGPTL8) rs2278426 single nucleotide polymorphism (SNP) and several environmental factors with serum lipid profiles in the Mulao and Han populations. A total of 879 individuals of the Mulao ethnic group and 865 individuals of the Han Chinese ethnic group were included. The serum apolipoprotein (Apo) B level was higher, however the serum ApoA1 level was lower in the Mulao individuals than in the Han individuals (P<0.05 and P<0.001, respectively). The genotypic and allelic frequencies, and the association with the ANGPTL8 rs2278426 SNP were different between the Mulao and Han populations. The frequency of the A allele was 17.80% in Han individuals and 23.04% in Mulao individuals (P<0.001). The frequencies of GG, GA and AA genotypes were 68.79, 26.82 and 4.39% in the Han population, and 60.64, 32.65 and 6.71% in the Mulao population (P<0.005), respectively. A significant association between the SNP and serum lipid traits was only detected in Han females and not in Han males or in the Mulao population. The subjects with GA/AA genotypes had lower low-density lipoprotein cholesterol (LDL-C) and ApoB levels, and higher ApoA1 levels with a higher ApoA1/ApoB ratio than the subjects with the GG genotype in the Han population. Subgroup analyses revealed that the subjects with the GA/AA genotype had lower levels of total cholesterol, LDL-C and ApoB, and a higher ApoA1/ApoB ratio than the subjects with the GG genotype in Han females (P<0.05-P<0.001). Serum lipid parameters were also associated with several environmental factors, including dietary patterns, lifestyle, obesity, physical inactivity and hypertension, in the two ethnic groups (P<0.05-0.001). These findings suggest that there may be an ethnic- and gender-specific association of the rs2278426 SNP and serum lipid parameters.

Gender-specific association between the cytoplasmic poly(A) binding protein 4 rs4660293 single nucleotide polymorphism and serum lipid levels.

Cytoplasmic poly(A) binding protein 4 (PABPC4) is an RNA-processing protein which has an important role in regulating gene expression. The association of the PABPC4 rs4660293 single nucleotide polymorphism (SNP) and serum lipid profiles has, to the best of our knowledge, not previously been studied in the Chinese population. The present study aimed to investigate the association between the PABPC4 rs4660293 SNP and several environmental factors with serum lipid levels in the Mulao and Han populations. A total of 727 individuals of Mulao nationality and 729 individuals of Han nationality were randomly selected from stratified randomized samples from a previous study by our group. Genotypes of the PABPC4 rs4660293 SNP were determined via polymerase chain reaction and restriction fragment length polymorphism analyses and subsequently confirmed by direct sequencing. Serum levels of low-density lipoprotein cholesterol (LDL-C) and apolipoprotein (Apo) B were higher in the Mulao group than those in the Han group (P<0.01 for each). The genotypic and allelic frequencies of the PABPC4 rs4660293 SNP were significantly different between males and females in the Mulao population (P<0.05 for each), while no significant difference was detected between those of males and females amongst the Han population. The frequency of the G allele was higher in Mulao males than in Mulao females (22.12 vs. 13.44%). The G allele carriers were found to have higher total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and ApoAI levels in Han females but not in Han males, and lower TC and HDL-C levels in Mulao females but not in Mulao males than those of the G allele non-carriers (P<0.05 for all). These associations were confirmed by multiple linear regression analysis (P<0.05–0.001). Serum lipid parameters were also correlated with multiple environmental factors (P<0.05–0.001). The PABPC4 rs4660293 SNP was associated with serum TC, HDL-C, LDL-C and ApoAI levels in these study populations; however, the association varied between the Mulao and Han populations. A gender-specific association was identified in the populations of the two ethnic groups.

New potential role of serum apolipoprotein E mediated by its binding to clumping factor A during Staphylococcus aureus invasive infections to humans.

Staphylococcus aureus is a crucial human pathogen expressing various immune-evasion proteins that interact with the host-cell molecules. Clumping factor A (ClfA) is a microbial surface protein that promotes S. aureus binding to fibrinogen, and is associated with septic arthritis and infective endocarditis. In order to identify the major human serum proteins that bind the ClfA, we utilized recombinant ClfA region A in a plate-based assay. SDS-PAGE analysis of the bound proteins yielded five prominent bands, which were analysed by MS yielding apolipoprotein E (ApoE) as the predominant protein. ClfA-sufficient S. aureus bound purified ApoE by more than one log greater than an isogenic ClfA-deficient mutant. An immunodot-blot assay yielded a linearity model for ClfA binding to human ApoE with a stoichiometric-binding ratio of 1.702 at maximal Pearson's correlation coefficient (0.927). These data suggest that ApoE could be a major and novel binding target for the S. aureus virulence factor ClfA. Thus, ClfA recruitment of serum ApoE to the S. aureus surface may sequester ApoE and blunt its host defence function against S. aureus-invasive infections to humans. In this context, compounds that can block or suppress ClfA binding to ApoE might be utilized as prophylactic or therapeutic agents.

Allergies respiratoires professionnelles aux épices et aromates

Atherosclerosis is studied in models with dysfunctional lipid homeostasis—predominantly the ApoE−/− mouse. The role of antigen-presenting cells (APCs) for lipid homeostasis is not clear. Using a LacZ reporter mouse, we showed that CD11c+ cells were enriched in aortae of ApoE−/− mice. Systemic long-term depletion of CD11c+ cells in ApoE−/− mice resulted in significantly increased plaque formation associated with reduced serum ApoE levels. In CD11ccre+ApoEfl/fl and Albumincre+ApoEfl/fl mice, we could show that ≈70% of ApoE is liver-derived and ≈25% originates from CD11c+ cells associated with significantly increased atherosclerotic plaque burden in both strains. Exposure to acLDL promoted cholesterol efflux from CD11c+ cells and cell-specific deletion of ApoE resulted in increased inflammation reflected by increased IL-1β serum levels. Our results determined for the first time the level of ApoE originating from CD11c+ cells and demonstrated that CD11c+ cells ameliorate atherosclerosis by the secretion of ApoE.

Antioxidant properties of high-density lipoproteins are impaired in women with polycystic ovary syndrome

To determine the relationships among the inflammatory index, intrinsic oxidation levels, lipid and apolipoprotein (apo)A-I concentrations of high-density lipoprotein (HDL), and polycystic ovary syndrome (PCOS). Cross-sectional study. University hospital. A total of 425 patients with PCOS and 441 control women were included. None. The HDL inflammatory index (HII) was determined using a cell-free fluorometric assay. Intrinsic HDL oxidation levels, HDL-free cholesterol, HDL-cholesterol ester, HDL-triglyceride, serum apoA-I, and malondialdehyde levels were also measured. The mean HII value and the frequency of HII ≥1 were significantly higher in the PCOS group (0.77 ± 0.54, 27.1%) than in the control group (0.53 ± 0.37, 8.4%). These values were also higher in each of the 4 PCOS phenotypes based on the Rotterdam criteria than in the controls, and higher in patients with hyperandrogenism (HA) + oligo- and/or anovulation (OA) phenotype than in those with OA + polycystic ovary (PCO) phenotype. Furthermore, patients with PCOS with OA + PCO had lower malondialdehyde and intrinsic HDL oxidation levels compared with those with HA. Multivariate regression analysis demonstrated that PCOS, HDL-cholesterol ester, and E2 levels were the main predictors of HII value. The impairment of HDL antioxidant/anti-inflammatory function in PCOS is related to HA status, increased oxidative stress, and abnormalities in HDL components and thus may contribute to PCOS pathogenesis and increase the risks of future cardiovascular diseases.

Leptin levels and lipoprotein profiles in patients with cholelithiasis.

To determine the relationships between serum leptin and levels of lipoprotein(a) [Lp(a)], apolipoprotein A-1 (ApoA-1) and apolipoprotein B (ApoB) in patients with cholelithiasis. Patients with ultrasound-confirmed cholelithiasis and controls frequency-matched for age, sex, body mass index, fasting blood glucose and haemoglobin A1c levels were recruited. Fasting blood samples from all study participants were assayed for glucose, haemoglobin A1c, total cholesterol, high density lipoprotein-cholesterol (HDL-C) and triglyceride. Serum Lp(a), ApoA-1 and ApoB levels were measured using nephelometric assays; serum leptin was measured using an enzyme-linked immunosorbent assay. A total of 90 patients with cholelithiasis and 50 controls were included in the study. Serum levels of leptin, Lp(a), total cholesterol, triglyceride and ApoB were significantly increased, and levels of ApoA-1 and HDL-C were significantly decreased, in patients with cholelithiasis compared with controls. Serum leptin in patients with cholelithiasis were significantly positively correlated with Lp(a) and ApoB and negatively correlated with ApoA-1. Patients with cholelithiasis have higher leptin levels and an altered lipoprotein profile compared with controls, with increased leptin levels being associated with increased Lp(a) and ApoB levels, and decreased ApoA-1 levels, in those with cholelithiasis.

Case report: A novel apolipoprotein A-I missense mutation apoA-I (Arg149Ser)Boston associated with decreased lecithin-cholesterol acyltransferase activation and cellular cholesterol efflux

We report a novel heterozygous apolipoprotein A-I (apoA-I) missense mutation (c.517C>A, p.Arg149Ser, designated as apoA-IBoston) in a 67-year-old woman and her 2 sons, who had mean serum high-density lipoprotein (HDL) cholesterol, apoA-I, and apoA-I in very large α-1 HDL that were 10%, 35%, and 16% of normal, respectively (all P < .05). The percentage of HDL cholesterol in the esterified form was also significantly (P < .05) reduced to 52% of control values. Cholesteryl ester tranfer protein (CETP) activity was normal. The mean global, adenosine triphosphate (ATP)-binding cassette transporter A1 and scavenger receptor B type I–mediated cellular cholesterol efflux capacity in apoB-depleted serum from affected family members were 41%, 37%, 47%, 54%, and 48% of control values, respectively (all P < .05). lecithin-cholesterol acyltransferase (LCAT) activity in plasma was 71% of controls, whereas in the cell-based assay, it was 73% of control values (P < .05). The data indicate that this novel apoA-I missense is associated with markedly decreased levels of HDL cholesterol and very large α-1 HDL, as well as decreased serum cellular cholesterol efflux and LCAT activity, but not with premature coronary heart disease, similar to other apoA-I mutations that have been associated with decreased LCAT activity.