OBJECTIVETo explore the dynamic changes of fetuin-A expression and the influences of the changes on liver damage, hepatocyte apoptosis and inflammation in a mouse fulminant hepatic failure (FHF) model.

METHODSThe changes of fetuin-A expression were investigated by semi-quantitative RT-PCR and Western blot. Immunohistochemical staining was used in TNFa and fetuin-A detection. Hepatocyte apoptosis was detected by TUNEL.

RESULTSFetuin-A mRNA expression decreased after the FHF model was established for 3 hours (compared with the normal group, P less than 0.01), while the protein expression decreased after nine hours (compared with the normal group, P less than 0.01). Fetuin-A expressions were negatively correlated with the liver pathological scores and TNFa levels.

CONCLUSIONIn our mouse FHF model, fetuin-A is a possible protective factor for liver damage.

Animals ; Blood Proteins ; metabolism ; Female ; Liver ; metabolism ; pathology ; Liver Failure ; metabolism ; pathology ; Mice ; Mice, Inbred BALB C ; alpha-2-HS-Glycoprotein

BACKGROUND: Coronary artery calcification is frequently seen in hemodialysis patients. The development and progression of coronary artery calcification is similar to osteogenesis, and a naturally occurring serum inhibitor of calcification may be involved. The aim of this study was to evaluate the relationship between coronary artery calcification, bone remodeling related factor, serum osteoprotegerin (OPG), calcification inhibitor and the serum fetuin-A levels in hemodialysis patients. METHODS: A total of 51 hemodialysis patient were assessed for their coronary artery calcium (CAC) scores with using multirow spiral computed tomography and measuring the serum OPG level, the serum fetuin-A level, the biochemical markers of inflammation, the lipid profile and the mineral metabolism. RESULTS: The mean serum OPG level was 3,561+/-1,160 pg/mL and the mean serum fetuin-A level was 28.5+/-4.1 mg/dL. The CAC scores were significantly correlated with the duration of dialysis (p=0.0225), hs-CRP (p=0.0392), serum phosphate (p=0.0341), Ca x P (p=0.0434), the serum OPG level (p=0.0026) and LDL-cholesterol (p=0.0438), after adjusting for age, gender, BMI, smoking history and the presence of diabetes. Multiple regression analysis showed that the CAC scores were significantly associated with the serum OPG level (p<0.0001) and the serum phosphate level (p=0.0003). The subgroup of the patients with a CAC score greater than 400 (the severe CAC group) had significantly higher OPG levels and lower fetuin-A levels than the groups of the patients with lower CAC scores. CONCLUSIONS: Our data suggest that the CAC scores in the patients undergoing hemodialysis were related with higher serum OPG and higher serum phosphate levels. The serum fetuin-A level was significantly lower in the patients with severe coronary artery calcification.
alpha-2-HS-Glycoprotein* ; Biomarkers ; Bone Remodeling ; Calcium ; Coronary Disease ; Coronary Vessels* ; Dialysis ; Humans ; Inflammation ; Kidney Failure, Chronic* ; Metabolism ; Osteogenesis ; Osteoprotegerin* ; Renal Dialysis ; Smoke ; Smoking ; Tomography, Spiral Computed

OBJECTIVETo identify the single nucleotide polymorphisms (SNPs) of the alpha2-Heremans-Schmid glycoprotein (AHSG) gene and assess their association with the AHSG serum level.

METHODSThe SNPs of the AHSG gene were identified from 30 unrelated Han individuals from Guangzhou area by resequencing. Linkage disequilibrium(LD) was performed to observe the linkage disequilibrium pattern. Then tagSNPs were genotyped in 192 Han individuals from Beijing and 424 Han individuals from Guangzhou area. Finally, luciferase reporter gene assay was performed to determine whether the SNPs affected the promoter activity. Serum AHSG concentrations were measured in the 192 subjects from Beijing using ELISA.

RESULTSEight SNPs were detected in total. The linkage disequilibrium profile in the Guangzhou Han population was different from that in the Beijing Han population. However, the allele and genotype frequencies of tagSNPs between the two Han populations were not significantly different. The reporter gene assay showed that the -799A allele had significantly higher promoter activity than the -799T allele. Multiple regression analysis revealed that only the rs2248690 SNP was an independent contributor to serum AHAG concentration.

CONCLUSIONThe rs2248690 SNP in the promoter region of the AHSG gene might affect the AHSG gene transcription.

Blood Proteins ; genetics ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Genotype ; Linkage Disequilibrium ; Polymorphism, Single Nucleotide ; genetics ; Serum ; chemistry ; alpha-2-HS-Glycoprotein

OBJECTIVETo examine the relationship between reduction of serum fetuin A and coronary artery calcification (CAC) in patients starting hemodialysis.

METHODSTwenty-nine patients on chronic hemodialysis (duration of hemodialysis less than 6 months) were enrolled in this study. Serum fetuin A and such potential CAC-related risk factors as C-reactive protein (CRP), Ca, P, iPTH, body mass index (BMI) were examined. CAC was detected by multislice spiral CT scan (MSCT) and quantified by the modified Agaston's scoring system. All the 29 patients were followed up for 18 months to appraise the cardiovascular events defined as cardiac failure, angina pectoris or myocardial infarction.

RESULTSEleven patients (78.57%) were found to have CAC as detected by MSCT in low serum fetuin A (below the average serum concentration of 0.71 g/L) group, a rate significantly higher than that in high serum fetuin A group (7 patients, 46.67%, P<0.05). Serum fetuin A in these 29 patients was related with CAC score (Pearson correlation coefficient of -0.734, P=0.001) and stepwise regression analysis indicated that serum fetuin A (standardized beta=-0.568, P=0.003) and age (standardized beta=0.416, P=0.019) were independently correlated to CAC. Such factors as CRP, Ca, P, iPTH, Chol, TG, HDL-C, LDL-C, BMI and blood pressure were excluded from the regression equation. Reduction of serum fetuin A was associated with cardiovascular events (Spearman's rho -0.758, P<0.01). No significant difference was found between low and high serum fetuin A groups by Kaplan-Meier survival analysis (P=0.065).

CONCLUSIONReduced serum fetuin A may be a potential risk factor of coronary artery calcification, and can contribute to cardiovascular events in patients starting hemodialysis.

Adult ; Aged ; Blood Proteins ; metabolism ; Calcinosis ; blood ; etiology ; Coronary Vessels ; pathology ; Female ; Humans ; Male ; Middle Aged ; Renal Dialysis ; adverse effects ; Risk Factors ; alpha-2-HS-Glycoprotein

OBJECTIVETo investigate the association of fetuin-A with residual renal function and carotid artery calcification in patients with chronic kidney disease (CKD).

METHODSBlood examples were collected form 60 CKD patients in stages CKD3 to CKD5 (20 patients per stage) for measurement of serum fetuin-A, albumin, calcium, phosphorus and parathyroid hormone, cholesterol, triglycercide, low-density lipoprotein, and high-density lipoprotein. MDRD equation was used to calculate the estimated glomerular filtration rate (eGFR), and ELISA was used to detect serum fetuin-A. Color Doppler ultrasound was performed to measure carotid intima-media thickness (CIMT).

RESULTSAs the eGFR decreased, serum fetuin-A significantly decreased in CKD5 stage compared with that in CKD4 stage (P<0.05); compared with that in CKD3 stage, serum fetuin-A level was significantly lowered in CKD4 stage (P<0.05). Linear regression analysis suggested a significant positive correlation between fetuin-A and eGFR. The rate of carotid artery calcification was the highest in CKD5 stage. Rank correlation analysis showed a negative correlation between fetuin-A and cIMT, and logistic regression analysis identified decreased serum Fetuin-A as a risk factor of carotid artery calcification.

CONCLUSIONSerum fetuin-A decreases following the decrease in eGFR, and decreased serum Fetuin-A level is a risk factor of carotid artery calcification in CKD patients.

Adult ; Calcinosis ; etiology ; Carotid Artery Diseases ; etiology ; Carotid Intima-Media Thickness ; Female ; Glomerular Filtration Rate ; Humans ; Male ; Middle Aged ; Renal Insufficiency, Chronic ; blood ; complications ; physiopathology ; Risk Factors ; alpha-2-HS-Glycoprotein ; metabolism

Preeclapsia (PE) is a severe disorder that occurs during pregnancy, leading to maternal and fetal morbidity and mortality. PE affects about 3-8% of all pregnancies. In this study, we conducted liquid chromatographymass spectrometry/mass spectrometry (LC-MS/MS) to analyze serum samples depleted of the six most abundant proteins from normal and PE-affected pregnancies to profile serum proteins. A total of 237 proteins were confidently identified with < 1% false discovery rate from the two groups of duplicate analysis. The expression levels of those identified proteins were compared semiquantitatively by spectral counting. To further validate the candidate proteins with a quantitative mass spectrometric method, selective reaction monitoring (SRM) and enzyme linked immune assay (ELISA) of serum samples collected from pregnant women with severe PE (n = 8) or normal pregnant women (n = 5) was conducted. alpha2-HS-glycoprotein (AHSG), retinol binding protein 4 (RBP4) and alpha-1-microglobulin/bikunin (AMBP) and Insulin like growth factor binding protein, acid labile subunit (IGFBP-ALS) were confirmed to be differentially expressed in PE using SRM (P < 0.05). Among these proteins, AHSG was verified by ELISA and showed a statistically significant increase in PE samples when compared to controls.
Adult ; Alpha-Globulins/metabolism ; Amino Acid Sequence ; Biological Markers/blood ; Blood Proteins/*analysis ; Case-Control Studies ; Female ; Humans ; Insulin-Like Growth Factor Binding Proteins/blood ; Molecular Sequence Data ; Pre-Eclampsia/*blood/diagnosis ; Pregnancy ; Proteome/*analysis ; Retinol-Binding Proteins, Plasma/metabolism ; alpha-2-HS-Glycoprotein/metabolism

BACKGROUND/AIMS: We assessed changes in hemodynamic and arterial stiffness parameters following reductions of dialysate calcium concentrations in patients undergoing hemodialysis. METHODS: In this prospective study, 20 patients on maintenance hemodialysis (10 females, 10 males) with dialysate calcium concentrations of 1.75 mmol/L were enrolled. At the start of the study, the dialysate calcium level was lowered to 1.50 mmol/L. Serial changes in biochemical, hemodynamic, and arterial stiffness parameters, including pulse wave velocity (PWV) and augmentation index (AIx), were assessed every 2 months for 6 months. We also examined changes in the calcification-inhibitory protein, serum fetuin-A. RESULTS: During the 6-month study period, serum total calcium and ionized calcium decreased consistently (9.5 +/- 1.0 to 9.0 +/- 0.7, p = 0.002 vs. 1.3 +/- 0.1 to 1.1 +/- 0.1, p = 0.035). Although no apparent changes in blood pressure were observed, heart-femoral PWW (hf-PWV) and AIx showed significant improvement (p = 0.012, 0.043, respectively). Repeated-measures ANOVA indicated a significant effect of lowering dialysate calcium on hf-PWV (F = 4.58, p = 0.004) and AIx (F = 2.55, p = 0.049). Accompanying the change in serum calcium, serum fetuin-A levels significantly increased (95.8 +/- 45.8 pmol/mL at baseline to 124.9 +/- 82.2 pmol/mL at 6 months, p = 0.043). CONCLUSIONS: Lowering dialysate calcium concentration significantly improved arterial stiffness parameters, which may have been associated with upregulation of serum fetuin-A.
Aged ; Analysis of Variance ; Ankle Brachial Index ; Arteries/*drug effects/physiopathology ; Biological Markers/blood ; Blood Pressure/drug effects ; Calcium/*administration & dosage/adverse effects ; Compliance ; Female ; Hemodialysis Solutions/*administration & dosage/adverse effects/chemistry ; Humans ; Male ; Middle Aged ; Prospective Studies ; Pulsatile Flow/*drug effects ; *Renal Dialysis ; Republic of Korea ; Time Factors ; Treatment Outcome ; alpha-2-HS-Glycoprotein/metabolism