Effects of Recombinant Human Lecithin Cholesterol Acyltransferase on Lipoprotein Metabolism in Humans.

BACKGROUND: LCAT (lecithin cholesterol acyl transferase) catalyzes the conversion of unesterified, or free cholesterol, to cholesteryl ester, which moves from the surface of HDL (high-density lipoprotein) into the neutral lipid core. As this iterative process continues, nascent lipid-poor HDL is converted to a series of larger, spherical cholesteryl ester-enriched HDL particles that can be cleared by the liver in a process that has been termed reverse cholesterol transport. METHODS: We conducted a randomized, placebocontrolled, crossover study in 5 volunteers with atherosclerotic cardiovascular disease, to examine the effects of an acute increase of recombinant human (rh) LCAT via intravenous administration (300-mg loading dose followed by 150 mg at 48 hours) on the in vivo metabolism of HDL APO (apolipoprotein)A1 and APOA2, and the APOB100-lipoproteins, very low density, intermediate density, and low-density lipoproteins. RESULTS: As expected, recombinant human LCAT treatment significantly increased HDL-cholesterol (34.9 mg/dL; P≤0.001), and this was mostly due to the increase in cholesteryl ester content (33.0 mg/dL; P=0.014). This change did not affect the fractional clearance or production rates of HDL-APOA1 and HDL-APOA2. There were also no significant changes in the metabolism of APOB100-lipoproteins. CONCLUSIONS: Our results suggest that an acute increase in LCAT activity drives greater flux of cholesteryl ester through the reverse cholesterol transport pathway without significantly altering the clearance and production of the main HDL proteins and without affecting the metabolism of APOB100-lipoproteins. Long-term elevations of LCAT might, therefore, have beneficial effects on total body cholesterol balance and atherogenesis.

Insights into the Structural Basis of Amyloid Resistance Provided by Cryo-EM Structures of AApoAII Amyloid Fibrils.

Amyloid resistance is the inability or the reduced susceptibility of an organism to develop amyloidosis. In this study we have analysed the molecular basis of the resistance to systemic AApoAII amyloidosis, which arises from the formation of amyloid fibrils from apolipoprotein A-II (ApoA-II). The disease affects humans and animals, including SAMR1C mice that express the C allele of ApoA-II protein, whereas other mouse strains are resistant to development of amyloidosis due to the expression of other ApoA-II alleles, such as ApoA-IIF. Using cryo-electron microscopy, molecular dynamics simulations and other methods, we have determined the structures of pathogenic AApoAII amyloid fibrils from SAMR1C mice and analysed the structural effects of ApoA-IIF-specific mutational changes. Our data show that these changes render ApoA-IIF incompatible with the specific fibril morphologies, with which ApoA-II protein can become pathogenic in vivo.

Proteomic Biomarkers of Intrahepatic Cholestasis of Pregnancy.

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disease, which can lead to adverse fetal outcomes, including preterm labor and intrauterine death. The pathogenesis of ICP is still unclear. We hypothesized that pathological index leads to abnormal placenta changes in ICP. Investigation of these differences in protein expression in parallel profiling is essential to understand the comprehensive pathophysiological mechanism underlying ICP. The present study screened differentially expressed proteins (DEPs) as novel diagnostic markers for ICP. Proteomic profiles of placental tissues from 32 ICP patients and 24 healthy volunteers (controls) were analyzed. Our founding was valid by following western blotting and immunohistochemistry staining, respectively. The association of the key protein expression with clinicopathological features of ICP was further analyzed. A total of 178 DEPs were identified between the ICP and control groups. Functional enrichment analysis showed these proteins were significantly enriched in the PPAR singling pathway by KEGG and PPARα/RXRα activation by IPA. Apolipoprotein A2 (APOA2) was the only upregulated protein, which uniquely identified in ICP groups and related to both pathways. Validation of western blotting and immunohistochemical staining analysis showed significantly higher APOA2 expression in the ICP group than in the control group. Furthermore, the expression of APOA2 is associated with clinicopathological features in ICP groups. Receiver operating characteristic (ROC) curve analyses showed that the AUC of APOA2 was 0.8984 (95% confidence interval (CI): 0.772-1.000). This study has identified up-regulated APOA2 associated with PPAR singling pathway and PPARα/RXRα activation in ICP. Thus, APOA2 may be involved in ICP pathogenesis, serving as a novel biomarker for its diagnosis.

Clinical development of a blood biomarker using apolipoprotein-A2 isoforms for early detection of pancreatic cancer.

BACKGROUND: We have previously reported apolipoprotein A2-isoforms (apoA2-is) as candidate plasma biomarkers for early-stage pancreatic cancer. The aim of this study was the clinical development of apoA2-is. METHODS: We established a new enzyme-linked immunosorbent sandwich assay for apoA2-is under the Japanese medical device Quality Management System requirements and performed in vitro diagnostic tests with prespecified end points using 2732 plasma samples. The clinical equivalence and significance of apoA2-is were compared with CA19-9. RESULTS: The point estimate of the area under the curve to distinguish between pancreatic cancer (n = 106) and healthy controls (n = 106) was higher for apoA2-ATQ/AT [0.879, 95% confidence interval (CI): 0.832-0.925] than for CA19-9 (0.849, 95% CI 0.793-0.905) and achieved the primary end point. The cutoff apoA2-ATQ/AT of 59.5 µg/mL was defined based on a specificity of 95% in 2000 healthy samples, and the reliability of specificities was confirmed in two independent healthy cohorts as 95.3% (n = 106, 95% CI 89.4-98.0%) and 95.8% (n = 400, 95% CI 93.3-97.3%). The sensitivities of apoA2-ATQ/AT for detecting both stage I (47.4%) and I/II (50%) pancreatic cancers were higher than those of CA19-9 (36.8% and 46.7%, respectively). The combination of apoA2-ATQ/AT (cutoff, 59.5 µg/mL) and CA19-9 (37 U/mL) increased the sensitivity for pancreatic cancer to 87.7% compared with 69.8% for CA19-9 alone. The clinical performance of apoA2-is was blindly confirmed by the National Cancer Institute Early Detection Research Network. CONCLUSIONS: The clinical performance of ApoA2-ATQ/AT as a blood biomarker is equivalent to or better than that of CA19-9.

Rapid Changes in Serum Lipid Profiles during Combination Therapy with Daclatasvir and Asunaprevir in Patients Infected with Hepatitis C Virus Genotype 1b

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.

APO A2 -265T/C Polymorphism Is Associated with Increased Inflammatory Responses in Patients with Type 2 Diabetes Mellitus

BACKGROUND: Apolipoprotein A2 (APO A2) is the second most abundant structural apolipoprotein in high density lipoprotein. Several studies have examined the possible effect of APO A2 on atherosclerosis incidence. Due to the role of inflammation in atherosclerosis, we aimed to determine the relationship between APO A2 -265T/C polymorphism and inflammation as a risk factor in type 2 diabetes mellitus (T2DM) patients. METHODS: In total, 180 T2DM patients, with known APO A2 -265T/C polymorphism, were recruited for this comparative study and were grouped equally based on their genotypes. Dietary intakes, anthropometric parameters, lipid profile, and inflammatory markers (i.e., pentraxin 3 [PTX3], high-sensitivity C-reactive protein [hs-CRP], and interleukin 18) were measured. The data were analyzed using an independent t-test, a chi-square test, and the analysis of covariance. RESULTS: After adjusting for confounding factors, in the entire study population and in the patients with or without obesity, the patients with the CC genotype showed higher hs-CRP (P=0.001, P=0.008, and P=0.01, respectively) and lower PTX3 (P=0.01, P=0.03, and P=0.04, respectively) in comparison with the T allele carriers. In the patients with the CC genotype, no significant differences were observed in the inflammatory markers between the obese or non-obese patients. However, regarding the T allele carriers, the plasma hs-CRP level was significantly higher in the obese patients compared to the non-obese patients (P=0.01). CONCLUSION: In the T2DM patients, the CC genotype could be considered as a risk factor and the T allele as a protective agent against inflammation, which the latter effect might be impaired by obesity. Our results confirmed the anti-atherogenic effect of APO A2, though more studies are required to establish this effect.

Diagnostic Value of Combining Tumor and Inflammatory Markers in Lung Cancer

BACKGROUND: Despite major advances in lung cancer treatment, early detection remains the most promising way of improving outcomes. To detect lung cancer in earlier stages, many serum biomarkers have been tested. Unfortunately, no single biomarker can reliably detect lung cancer. We combined a set of 2 tumor markers and 4 inflammatory or metabolic markers and tried to validate the diagnostic performance in lung cancer. METHODS: We collected serum samples from 355 lung cancer patients and 590 control subjects and divided them into training and validation datasets. After measuring serum levels of 6 biomarkers (human epididymis secretory protein 4 [HE4], carcinoembryonic antigen [CEA], regulated on activation, normal T cell expressed and secreted [RANTES], apolipoprotein A2 [ApoA2], transthyretin [TTR], and secretory vascular cell adhesion molecule-1 [sVCAM-1]), we tested various sets of biomarkers for their diagnostic performance in lung cancer. RESULTS: In a training dataset, the area under the curve (AUC) values were 0.821 for HE4, 0.753 for CEA, 0.858 for RANTES, 0.867 for ApoA2, 0.830 for TTR, and 0.552 for sVCAM-1. A model using all 6 biomarkers and age yielded an AUC value of 0.986 and sensitivity of 93.2% (cutoff at specificity 94%). Applying this model to the validation dataset showed similar results. The AUC value of the model was 0.988, with sensitivity of 93.33% and specificity of 92.00% at the same cutoff point used in the validation dataset. Analyses by stages and histologic subtypes all yielded similar results. CONCLUSIONS: Combining multiple tumor and systemic inflammatory markers proved to be a valid strategy in the diagnosis of lung cancer.

Proteomic data show an increase in autoantibodies and alpha-fetoprotein and a decrease in apolipoprotein A-II with time in sera from senescence-accelerated mice

We evaluated changes in levels by comparing serum proteins in senescence-accelerated mouse-prone 8 (SAMP8) mice at 2, 6, 12, and 15 months of age (SAMP8-2 m, -6 m, -12 m, -15 m) to age-matched SAM-resistant 1 (SAMR1) mice. Mice were sacrificed, and blood was analyzed by 2-dimensional electrophoresis combined with mass spectrometry. Five protein spots were present in all SAMP8 serum samples, but only appeared in SAMR1 samples at 15 months of age except for spot 3, which also showed a slight expression in SAMR1-12 m sera. Two proteins decreased in the sera from SAMP8-2 m, -6 m, and -12 m mice, and divided into 2 spots each in SAMP8-15 m sera. Thus, the total number of altered spots in SAMP8 sera was 7; of these, 4 were identified as Ig kappa chain V region (M-T413), chain A of an activity suppressing Fab fragment to cytochrome P450 aromatase (32C2_A), alpha-fetoprotein, and apolipoprotein A-II. M-T413 is a monoclonal CD4 antibody, which inhibits T cell proliferation. We found that M-T413 RNA level was significantly enhanced in splenocytes from SAMP8-2 m mice. This agreed with serum M-T413 protein alterations and a strikingly lower blood CD4+ T cell count in SAMP8 mice when compared to the age-matched SAMR1 mice, with the latter negatively correlating with serum M-T413 protein volume. Age-related changes in serum proteins favored an increase in autoantibodies and alpha-fetoprotein and a decrease of apolipoprotein A-II, which occurred in SAMP8 mice at 2 months of age and onwards. These proteins may serve as candidate biomarkers for early aging.

Discovery and identification of serum biomarkers of Wilms' tumor in mice using proteomics technology / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Wilms' tumor (nephroblastoma) is a cancer of the kidneys that occurs typically in children and rarely in adults. Early diagnosis is very important for the treatment and prognosis of the disease. The aim of our study was to discover and identify potential non-invasive and convenient biomarkers for the diagnosis of Wilms' tumor.</p><p><b>METHODS</b>Nude mice were used to construct a Wilms' tumor model by injecting nephroblastoma cells into their bilateral abdomen. We collected 94 serum samples from mice consisting of 45 samples with Wilms' tumor and 49 controls. The serum proteomic profiles of the samples were analyzed via surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. The candidate biomarkers were purified by high-performance liquid chromatography, identified by liquid chromatography-mass spectrometry, and validated using ProteinChip immunoassays.</p><p><b>RESULTS</b>We finally retrieved two differential proteins (m/z 4509.2; 6207.9), which were identified as apolipoprotein A-II and polyubiquitin, respectively. The expression of apolipoprotein A-II was higher in the Wilms' tumor group than in the control group (P < 0.01). By contrast, the expression of polyubiquitin was lower in the Wilms' tumor group than in the control group.</p><p><b>CONCLUSION</b>Apolipoprotein A-II and polyubiquitin may be used as potential biomarkers for nephroblastoma in children, and the analysis of apolipoprotein A-II may help diagnose and treat Wilms' tumor.</p>

The Association between Apolipoprotein A-II and Metabolic Syndrome in Korean Adults: A Comparison Study of Apolipoprotein A-I and Apolipoprotein B

BACKGROUND: Apolipoprotein A-II (apoA-II) is the second-most abundant apolipoprotein in human high-density lipoprotein and its role in cardio metabolic risk is not entirely clear. It has been suggested to have poor anti-atherogenic or even pro-atherogenic properties, but there are few studies on the possible role of apoA-II in Asian populations. The aim of this study is to evaluate the role of apoA-II in metabolic syndrome (MetS) compared with apolipoprotein A-I (apoA-I) and apolipoprotein B (apoB) in Korean adults. METHODS: We analyzed data from 244 adults who visited the Center for Health Promotion in Pusan National University Yangsan Hospital for routine health examinations. RESULTS: The mean apoB level was significantly higher, and the mean apoA-I level was significantly lower, in MetS; however, there was no significant difference in apoA-II levels (30.5+/-4.6 mg/dL vs. 31.2+/-4.6 mg/dL, P=0.261). ApoA-II levels were more positively correlated with apoA-I levels than apoB levels. ApoA-II levels were less negatively correlated with homocysteine and high sensitivity C-reactive protein levels than apoA-I levels. The differences in MetS prevalence from the lowest to highest quartile of apoA-II were not significant (9.0%, 5.7%, 4.9%, and 6.6%, P=0.279). The relative risk of the highest quartile of apoA-II compared with the lowest quartile also was not significantly different (odds ratio, 0.96; 95% confidence interval, 0.95 to 1.04; P=0.956). CONCLUSION: Compared with apoA-I (negative association with MetS) and apoB (positive association with MetS) levels, apoA-II levels did not show any association with MetS in this study involving Korean adults. However, apoA-II may have both anti-atherogenic and pro-atherogenic properties.

La apolipoproteína A-II altera la composición apolipoproteica de HDL y su capacidad para activar la lipoproteína lipasa / Apolipoprotein A-II affects HDL apolipoprotein composition and HDL-mediated lipoprotein lipase activation

Introducción La apolipoproteína (apo) A-II es la segunda proteína cuantitativamente más importante de las HDL; sin embargo su función es poco conocida. Los estudios realizados en humanos y ratones modificados genéticamente han demostrado un efecto de la apoA-II sobre el metabolismo de los triglicéridos. El objetivo principal de este estudio es analizar la relación entre la apoA-II y la composición apolipoproteica de las HDL así como la capacidad de estas lipoproteínas de modular la actividad de la enzima lipoproteína lipasa (LPL) y, por tanto, la concentración de triglicéridos. Métodos Se recogieron muestras de sangre en 32 voluntarios sanos tras 11h de ayuno. Se recogieron los datos antropométricos y se determinaron los parámetros lipídicos y apolipoproteicos. Las HDL aisladas por ultracentrifugación fueron incubadas con una emulsión radioactiva de triglicéridos y LPL bovina. En 14 de los voluntarios, se obtuvo una muestra adicional de sangre, 3h después de un desayuno. Resultados La concentración de apoA-II correlacionó de forma positiva con la concentración de triglicéridos (R=0,55, p<0,05) y de forma inversa con el cociente apoC-II+apoE/apoC-III en HDL (R=−0,43, p<0,05). La apoA-II también correlacionó inversamente con la capacidad de las HDL de modular la actividad LPL (R=−0,35, p<0,05). Por ultimo, la concentración de apoA-II correlacionó positivamente con los triglicéridos postprandiales (R=0,58, p<0,05).Conclusión Estos resultados sugieren que la apoA-II en HDL tiene un papel importante en la regulación del metabolismo de los triglicéridos y sugieren que, en parte, ello es debido a la alteración en la capacidad de las HDL de modular la actividad LPL (AU)

Introduction Apolipoprotein (apo)A-II is the second most abundant HDL protein but its function remains largely unknown. Studies in humans and genetically-modified mice have demonstrated a role for apoA-II in triglyceride metabolism. The main objective of this study was to evaluate the relationship between apoA-II and HDL apolipoprotein composition, as well as HDL-mediated lipoprotein lipase (LPL) coactivation and plasma triglyceride concentration.Methods Eleven-hour fasting blood samples were taken from 32 healthy volunteers. Anthropometric data and lipid and apolipoprotein parameters were analyzed. HDL isolated by ultracentrifugation was incubated in the presence of a triolein-based emulsion and bovine LPL. In 14 of these volunteers, an additional blood sample was taken 3h after breakfast.Results ApoA-II concentration was directly correlated with plasma triglycerides (R=0.55, p<0.05) and inversely correlated with the HDL-apoC-II+apoE/apoC-III ratio (R=−0.43, p<0.05). ApoA-II was also inversely correlated with HDL-mediated LPL coactivation (R=−0.35, p<0.05). ApoA-II concentration was directly correlated with plasma triglycerides 3h after the fat-loading test (R= 0.58, p<0.05).Conclusion These results show that HDL-apoA-II levels play a crucial role in triglyceride catabolism and suggest that, at least in part, this is due to modulation of LPL activity (AU)

The screening and identification of Apolipoprotein A-II from serum differential proteins in hepatocellular carcinoma patients / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To screen differential proteins in serum from hepatocellular carcinoma (HCC) patients by Proteomic Technology and to purify and identify them.</p><p><b>METHODS</b>Surface enhanced laser desorption Ionization time of flight-mass spectrum (SELDI-TOF-MS) was employed to screen differential proteins in serum from 33 HCC patients and 33 control cases, and then to purify and identify them using isoelectric precipitation, Tricine sodium dodecyl sulphate polyacrylamide gel electrophoresis (Tricine-SDS-PAGE) and high performance liquid chromatography tandem Mass Spectrum (HPLC-MS).</p><p><b>RESULTS</b>65 protein peaks in the range of relative molecular weight from 2,000 to 10,000 were found significant difference (P less than 0.05) between the patient group and control group. Based on these differential protein peaks, diagnostic model for HCC detection was established and its sensitivity and specificity were 100% and 96.97% respectively. Proteins with 8,706.5 and 8,579.2 relative molecular weights (the t value was 2.562 and 2.783 respectively, and P value was 0.013 and 0.015 respectively) out of the 65 differential proteins were purified and identified, and then recognized as Apolipoprotein AII (Apo AII).</p><p><b>CONCLUSION</b>Apo AII is probably a differential protein of HCC and maybe related to the pathogenesis of HCC.</p>

Gel electrophoresis analysis on plasma differential protein in patients with unstable angina of blood-stasis pattern / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To seek the plasma differential proteins in patients with unstable angina of blood-stasis pattern (UA-BSS) for exploring the proteomic specialty in them by way of two-dimensional difference gel electrophoresis (DIGE) detection on plasma of patients and healthy persons.</p><p><b>METHODS</b>Using DIGE and tandem mass spectrometry, comparative proteomic study was conducted on the plasma of 12 UA patients of qi-deficiency and blood-stasis pattern (UA-QBS), 12 UA patients of phlegm-stasis cross-blocking pattern (UA-PSS) and 12 healthy volunteers.</p><p><b>RESULTS</b>Preliminary results showed that Haptoglobin beta chain, DBP, HBB, HBA, Transthyretin, ApoA- I, ApoA-IV were significantly differentially expressed in both patterns, while Haptoglobin alpha1 chain, alpha-1-acid glycoprotein, ApoC-III, ApoA-II, ApoC-II, ApoJ, and Haptoglobin alpha 2 chain were only seen differentially expressed in the UA-PSS patients, alpha1-antitrypsin, Fibrinogen gamma chain, and Fibrin beta were only seen differentially expressed in UA-QBS patients.</p><p><b>CONCLUSION</b>The common proteomics characteristics of patients of QBS and PSS patterns may be correlated with inflammatory reaction and metabolic disturbance (including blood lipid and blood oxygen).</p>

Análisis del proteoma hepático de ratones transgénicos de apo A-II humana: identificación de proteínas potencialmente implicadas en la regulación del metabolismo de triglicéridos y la respuesta a la insulina / Analysis of the liver proteome of human apolipoprotein A-II transgenic mice: identification of proteins potentially involved in the regulation of triglyceride metabolism and insulin response

Introducción. La función de la apolipoproteína A-II (apo A-II) en el metabolismo lipoproteico y su relación con la arteriosclerosis es poco conocida. Los estudios realizados en humanos y ratones modificados genéticamente han demostrado un efecto directo de la apo A-II en el metabolismo de los triglicéridos y los ácidos grasos libres (AGL) y la sensibilidad a la insulina. El objetivo principal de este estudio es la identificación de proteínas diferencialmente expresadas en el hígado de ratones transgénicos de apo A-II humana (h) y su potencial relación con el metabolismo de los triglicéridos y la glucosa. Material y métodos. Se realizaron estudios metabólicos de las lipoproteínas ricas en triglicéridos, la betaoxidación hepática y la prueba de tolerancia a la glucosa en ratones transgénicos de apo A-IIh y en controles en situación de ayunas y tras una carga oral de aceite de oliva. Los cambios en el perfil de expresión proteica se analizaron mediante el análisis comparativo de geles bidimensionales y la identificación de proteínas mediante espectrometría de masas MALDI-TOF. Resultados. Los ratones transgénicos de apo A-IIh presentaban un incremento del colesterol y los triglicéridos de las lipoproteínas que contienen apo B, hipertrigliceridemia aumentada tras la carga oral de ácido oleico, así como un aclaramiento acelerado de la glucosa tras la prueba de sobrecarga de glucosa. Estos cambios estaban asociados a una reducción en el catabolismo de las lipoproteínas ricas en triglicéridos y la tasa de betaoxidación hepática, pero sin cambios significativos en la actividad de la lipoproteína lipasa. De las más de 1.000 manchas resueltas en el rango pH 3 a 10, se identificaron 55 alteraciones significativas en los ratones transgénicos en comparación con los ratones controles, 16 de las cuales estaban relacionadas directamente con el metabolismo de los AGL y los carbohidratos. Conclusiones. La sobreexpresión apo A-IIh en ratones transgénicos induce hipertrigliceridemia posprandial debido, al menos en parte, a un defecto en el catabolismo de las lipoproteínas ricas en triglicéridos. La aproximación proteómica nos ha permitido detectar y caracterizar diferencias en el proteoma hepático de los ratones transgénicos de apo A-IIh y establecer proteínas potencialmente involucradas en el metabolismo de los AGL. Se requieren más estudios bioquímicos y moleculares para investigar el significado funcional de los cambios encontrados (AU)

Introduction. The role of apolipoprotein A-II (apo A-II) in lipoprotein metabolism and its relationship with atherosclerosis is poorly understood. Several studies both in humans and genetically modified mice have shown a direct effect of apo A-II on triglyceride and free fatty acid (FFA) metabolism and on insulin sensitivity. The aim of this study was to identify the proteins differentially expressed in the livers of human apo A-II transgenic mice and their potential relationship with triglyceride and glucose metabolism. Matherial and methods. Metabolic studies of triglyceride-rich lipoproteins, liver beta-oxidation and the glucose tolerance test were conducted in C57BL/6 control mice and human apo A-II transgenic mice in both fasting and postprandial states. The changes in protein expression patterns were determined by analysis of two-dimensional polyacrylamide gel electrophoresis while protein identification was performed by mass spectrometry (MALDI-TOF). Results. Human apo A-II transgenic mice showed an increase in cholesterol and triglycerides from apo B-containing lipoproteins, a higher response after oral fat test with oleic acid and higher glucose clearance after the glucose test. These changes were associated with a reduction in the clearance of triglyceride-rich lipoproteins and in the rate of liver beta-oxidation, but there were no significant changes in lipoprotein lipase activity. Within the pH 3-10 range, 55 out of more than 1,000 spots were identified to be significantly altered in human apo A-II transgenic mice compared with control mice, and 16 of these spots were directly related with FFA and carbohydrate metabolism. Conclusions. Overexpression of human apo A-II in transgenic mice induces postprandial hypertriglyceridemia. This finding is at least partly due to reduced catabolism of triglyceride-rich lipoproteins. We have been able to detect and characterize differences in the liver proteome of human apo A-II transgenic mice and to identify proteins potentially related to FFA metabolism. Further biochemical and molecular studies are required to investigate the functional significance of the changes found (AU)

Lipid profiles in patients with systemic lupus erythematosus / 대한내과학회지

BACKGROUND: The aims of this study were the identification of the abnormalities in lipid profiles and the correlations between serum lipid profiles and inflammatory parameters in patients with systemic lupus erythematosus. METHODS: The subjects were 50 patients with systemic lupus erythematosus who have been treated in rheumatology clinic, Yeungnam University Hospital. Serum lipids and apolipoproteins were measured and compared with those of age- and sex-matched controls. In systemic lupus erythematosus group, disease activities were assessed by systemic lupus erythematosus disease activity index and erythrocyte sedimentation rate. RESULTS: All lipid profiles were within normal range but most of lipoprotein levels were higher in patients with systemic lupus erythematosus than controls. Triglyceride, low-density lipoprotein and very-low-density lipoprotein were statistically significant (p=0.001, p=0.023, and p=0.001 respectively). Total cholesterol and low-density lipoprotein were significantly increased in systemic lupus erythematosus patients with proteinuria (>or=100 mg/dL/24hr) than in patients without proteinuria. Total cholesterol and low-density lipoprotein had positive correlations and apolipoprotein A-II had negative correlation with systemic lupus erythematosus disease activity index. Low-density lipoprotein and apolipoprotein B had positive correlations, high-density lipoprotein and apolipoprotein A-II had negative correlations with erythrocyte sedimentation rate. But differences of lipid profiles according to the duration of disease and total doses of steroid were not significant. CONCLUSION: This study showed that triglyceride, low-density lipoprotein, and very-low-density lipoprotein in patients with systemic lupus erythematosus were higher than controls. Total cholesterol and LDL in patients with SLE had positive correlations with disease activities.

Valores de referencia de apoproteínas B100, A-I, A-II y E en mujeres premenopáusicas de la República Argentina / Reference values of apoproteins B100, A-I, A-II and E in premenopausal argentine women

Existe una relación epidemiológica entre el perfil apolipoproteico y el riesgo cardiovascular. Se han realizado pocos estudios en mujeres y menos aún en la mujeres premenopáusicas. Los objetivos del presente trabajo fueron determinar los valores de referencia en mujeres premenopáusicas clínicamente sanas de las apolipoproteínas B100, A-I, A-II y E, y correlacionarlos con los valores lipídicos de: colesterol de HDL Total (C-HDL Total), C-HDL2, C-HDL3, C-LDL y triglicéridos de VLDL (Tg-VLDL). Para ello se estudiaron 129 mujeres con perfil lipoproteico normal, de edades entre 37 y 50 años. Los valores de las apolipoproteínas fueron: apo B100: 1,17 ñ0,21 g/L (Media ñ 0,21 g/L (Media ñ DE), apo A-I: 1,34 ñ 0,24 g/L, apo A-II: 0,343 ñ 0,07 g/L y apo E: 0,065 ñ 0,017 g/L. Se obtuvieron: una media para C-HDL Total de 54,0 ñ 13,1 mg/dl, de C-HDL2 de 13,6 ñ 8,6 mg/dl y de C-HDL3 de 39,3 ñ 7,9 mg/dl. El C-LDL fue de 116,0 ñ 26,00 mg/dl. En este trabajo se informan por primera vez en Argentina los valores de referencia de concentración plasmática de apo B100, apo A-I vs C-HDL Total: 0,61 (p < 0,019), apo A-I vs C-HDL 2: 0,32 (p < 0,01), apo A-I vs C-HDL3: 0,52 (p < 0,01). La correlación de apo A-II vs C-HDL fue de 0,28 (p < 0,01). La correlación de apo E y Tg-VLDL fue de 0,25 (p < 0,025). Se calculó el índice de Breslow que evalúa el tamaño de HDL como cociente C-HDL/apo A-I + apo A-II expresados en moles, el valor obtenido fue de 21,06 ñ 4,08. Este coincide con las referencias sugiriendo que en la premenopáusica no hay cambio de tamaño en las HDL

Valores de referencia de apoproteínas B100, A-I, A-II y E en mujeres premenopáusicas de la República Argentina / Reference values of apoproteins B100, A-I, A-II and E in premenopausal argentine women

Existe una relación epidemiológica entre el perfil apolipoproteico y el riesgo cardiovascular. Se han realizado pocos estudios en mujeres y menos aún en la mujeres premenopáusicas. Los objetivos del presente trabajo fueron determinar los valores de referencia en mujeres premenopáusicas clínicamente sanas de las apolipoproteínas B100, A-I, A-II y E, y correlacionarlos con los valores lipídicos de: colesterol de HDL Total (C-HDL Total), C-HDL2, C-HDL3, C-LDL y triglicéridos de VLDL (Tg-VLDL). Para ello se estudiaron 129 mujeres con perfil lipoproteico normal, de edades entre 37 y 50 años. Los valores de las apolipoproteínas fueron: apo B100: 1,17 ñ0,21 g/L (Media ñ 0,21 g/L (Media ñ DE), apo A-I: 1,34 ñ 0,24 g/L, apo A-II: 0,343 ñ 0,07 g/L y apo E: 0,065 ñ 0,017 g/L. Se obtuvieron: una media para C-HDL Total de 54,0 ñ 13,1 mg/dl, de C-HDL2 de 13,6 ñ 8,6 mg/dl y de C-HDL3 de 39,3 ñ 7,9 mg/dl. El C-LDL fue de 116,0 ñ 26,00 mg/dl. En este trabajo se informan por primera vez en Argentina los valores de referencia de concentración plasmática de apo B100, apo A-I vs C-HDL Total: 0,61 (p < 0,019), apo A-I vs C-HDL 2: 0,32 (p < 0,01), apo A-I vs C-HDL3: 0,52 (p < 0,01). La correlación de apo A-II vs C-HDL fue de 0,28 (p < 0,01). La correlación de apo E y Tg-VLDL fue de 0,25 (p < 0,025). Se calculó el índice de Breslow que evalúa el tamaño de HDL como cociente C-HDL/apo A-I + apo A-II expresados en moles, el valor obtenido fue de 21,06 ñ 4,08. Este coincide con las referencias sugiriendo que en la premenopáusica no hay cambio de tamaño en las HDL (AU)