Objective: To investigate the predictive value of glycosylated hemoglobin A1c/apolipoprotein A-1 (HbA1c/ApoA-1) ratio for major adverse cardiovascular events (MACEs) in patients with acute coronary syndrome (ACS). Methods: The present study is a retrospective cohort study. ACS patients who were hospitalized and underwent coronary angiography at Beijing Hospital from March 2017 to March 2019 were enrolled. Baseline information such as sex, age, previous history, Gensini score, HbA1c and ApoA-1 were analyzed. Patients were divided into two groups according to presence or absence of MACEs and the difference on HbA1c/ApoA-1 ratio was compared between the two groups. According to the tertiles of HbA1c/ApoA-1 levels, patients were divided into high (5.87-16.12), medium (4.50-5.83) and low (2.11-4.48) HbA1c/ApoA-1 groups. Cox proportional risk model was used to evaluate the differences in MACEs and all-cause mortality among the three groups. Kaplan-Meier survival analysis was used to compare the differences of MACEs between the various HbA1c/ApoA-1 groups. Results: A total of 366 ACS patients were included in this study. The mean age of the patients was (65.9±10.3) years. There were 59 MACEs and 10 all-cause deaths during the mean of (22.3±4.4) months follow-up. After adjusting for age, systolic blood pressure, history of diabetes and Gensini score, the incidence of MACEs was 2.45 times higher in the high HbA1c/ApoA-1 group than in the low HbA1c/ApoA-1 group (95%<i>CIi> 1.16-5.18, <i>Pi>=0.019). There was no significant difference in all-cause mortality between the high and low HbA1c/ApoA-1 groups (<i>Pi>=1.000). Kaplan-Meier survival analysis showed that patients in the high HbA1c/ApoA-1 group had the highest risk of MACEs, while patients in the low HbA1c/ApoA-1 group had the lowest risk of MACEs (<i>Pi><0.01). Spearman rank correlation analysis showed that HbA1/ApoA-1 ratio was positively correlated with Gensini score in ACS patients (<i>ri>=0.274, <i>Pi><0.01). Conclusion: High HbA1c/ApoA-1 ratio was an independent risk factor for MACEs in ACS patients. Patients with high HbA1c/ApoA-1 ratio had more severe coronary artery disease lesions. HbA1c/ApoA-1 ratio may be used as a potential risk stratification biomarker for ACS patients, it might be useful for the early identification of high-risk population and for predicting the incidence of MACEs among ACS patients.
Aged ; Humans ; Middle Aged ; Acute Coronary Syndrome/diagnosis* ; Apolipoprotein A-I/analysis* ; Biomarkers/analysis* ; Glycated Hemoglobin/analysis* ; Percutaneous Coronary Intervention ; Retrospective Studies ; Risk Factors ; Predictive Value of Tests

PURPOSE: The present study aimed to investigate the value of apolipoproteins, including ApoA-1, ApoC-III, and ApoE, in patients with small cell lung cancer (SCLC) as potential biomarkers for diagnosis, prognosis, and cancer progression. MATERIALS AND METHODS: Lung samples were collected from 89 patients with SCLC. Nineteen lung samples from non-small cell lung cancer (NSCLC) patients and 12 normal lung tissues were used as controls. Expression profiles of ApoA-1, ApoC-III, and ApoE in different samples were examined using immunohistochemical methods, and the expression levels were correlated with cancer types, treatment, and outcomes using chi-square and Mann-Whitney tests. RESULTS: Expression of ApoA-1 and ApoC-III in SCLC was significantly different, compared with that in NSCLC and normal lung tissues, and was correlated with recurrence of SCLC. Patients undergoing neoadjuvant chemotherapy before surgery showed significantly reduced expression of ApoA-1 and increased expression of ApoC-III and ApoE. Nevertheless, the expression levels of ApoA-1, ApoC-III, and ApoE were not correlated with SCLC staging. CONCLUSION: ApoA-1 and ApoC-III may be used as differentiating and predictive markers for SCLC. ApoA-1, ApoC-III, and ApoE may be used to monitor the efficacy of chemotherapy.
Adult ; Aged ; Apolipoprotein A-I/*genetics ; Apolipoprotein C-III/*genetics ; Apolipoproteins E/*genetics ; Biomarkers/analysis ; Case-Control Studies ; Female ; Gene Expression Regulation ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Predictive Value of Tests ; Prognosis ; RNA, Messenger/*genetics ; Small Cell Lung Carcinoma/*diagnosis/genetics

BACKGROUNDABCA7 is a member of the ABCA subfamily that shows a high degree of homology to ABCA1 and, like ABCA1, mediates cellular cholesterol and phospholipid release by apolipoproteins when transfected in vitro. However, expression of ABCA7 has been shown to be downregulated by increased cellular cholesterol while ABCA1 was upregulated.

METHODSThe underlying mechanism for this effect was examined in ABCA1 or ABCA7-transfected HEC293. Lipid content in the medium and cells was determined by enzymatic assays. Gene expression was quantitated by real time PCR, and protein content was determined by Western blotting.

RESULTSWhile ABCA7 mRNA was decreased by 25-hydroxycholesterol treatment, ABCA1 was apparently increased. Treatment with the synthetic LXR agonist T0901317 (T09) upregulated ABCA1 expression and apoAI-mediated cellular lipid release in ABCA1-transfected HEC293 cells, but ABCA7 expression and cellular lipid release in ABCA7-transfected HEC293 cells showed no obvious changes.

CONCLUSIONThe ABCA7 gene is regulated by sterol in a direction opposite to that of ABCA1.

ATP Binding Cassette Transporter 1 ; analysis ; genetics ; physiology ; ATP-Binding Cassette Transporters ; analysis ; genetics ; physiology ; Amino Acid Sequence ; Apolipoprotein A-I ; physiology ; Gene Expression Regulation ; HEK293 Cells ; Humans ; Hydrocarbons, Fluorinated ; pharmacology ; Hydroxycholesterols ; pharmacology ; Lipid Metabolism ; Liver X Receptors ; Molecular Sequence Data ; Orphan Nuclear Receptors ; agonists ; Sulfonamides ; pharmacology

BACKGROUNDAlteration in the protein composition of high-density lipoprotein (HDL) has been proposed as a mechanism for the development of coronary heart disease (CHD). In HDL, an increase in serum amyloid A protein (SAA) accompanying the decrease in apolipoprotein A-I (apoA-I) has been found during the acute inflammation period. However, whether this phenomenon persists in CHD patients, a disease related to inflammation, is unknown. The purpose of the present study was to explore the relationship between SAA and apoA-I in HDL isolated from CHD patients.

METHODSOverall, 98 patients with confirmed stable CHD and 90 control subjects matched for age and gender were enrolled in this case-control study. Potassium bromide (KBr) density gradient ultracentrifugation was used to isolate HDL from plasma. The levels of SAA and apoA-I in the HDL samples were detected by enzyme-linked immunosorbent assay kits. Pearson's correlation and general linear models were used in the analysis.

RESULTSCompared with controls, patients with CHD had a significant decrease in the amount of apoA-I ((14.21 ± 8.44) µg/ml vs. (10.95 ± 5.95) µg/ml, P = 0.003) in HDL and a significant increase in the amount of log SAA (1.21 ± 0.46 vs. 1.51 ± 0.55, P < 0.00001). Differences were independent of age, body mass index (BMI), HDL cholesterol (HDL-C), and other factors. An independently and statistically significant positive correlation between log SAA and apoA-I in HDL was observed only in the CHD group (β = 2.0, P = 0.026). In the general linear model, changes in log(SAA), age, age2, gender, BMI and HDL-C could explain a statistically significant 43% of the variance in apoA-I.

CONCLUSIONSThis study provides direct evidence for the first time that there was an independent positive correlation between log SAA and apoA-I in the HDL of CHD patients, indicating the alteration of protein composition in HDL. However, the question of whether this alteration in HDL is associated with impairment of HDL functions requires further research.

Adult ; Aged ; Apolipoprotein A-I ; analysis ; Coronary Disease ; blood ; etiology ; Female ; Humans ; Lipoproteins, HDL ; analysis ; blood ; Male ; Middle Aged ; Serum Amyloid A Protein ; analysis

OBJECTIVE: To explore the association between apolipoprotein AI (ApoAI) gene rs12721026 polymorphism and cerebral hemorrhage (CH) in Changsha Han population, and to evaluate the effect of rs12721026 polymorphism on plasma lipid levels. METHODS: A total of 273 patients with CH and 140 healthy controls were collected. The rs12721026 polymorphism of ApoAI was analyzed by SNaPshot genotyping analysis and DNA sequencing. The total cholesterol (TG), triglyceride (TC), HDL-C and LDL-C were examined by oxidase method. RESULTS: There was no significant difference in the genotype and allele frequencies of rs12721026 polymorphism between the CH group and the control group (P>0.05). Both in the CH group and in the control group, the level of HDL-C of the TT gene type of rs12721026 was significantly higher than that of the GT/GG gene type (P<0.05). There was no significant difference in the levels of TG, TC and LDL-C among different subgroups of gene types. CONCLUSION There may be no association between apoAI gene rs12721026 polymorphism with CH in Changsha Han population, which may still influence the HDL-C levels.
Apolipoprotein A-I ; genetics ; Asian Continental Ancestry Group ; Case-Control Studies ; Cerebral Hemorrhage ; blood ; genetics ; Cholesterol ; blood ; Gene Frequency ; Genotype ; Humans ; Lipids ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA ; Triglycerides ; blood

ATP-binding cassette transporter A1 (ABCA1) promotes cholesterol and phospholipid efflux from cells to lipid-poor apolipoprotein A-I (apoA-I), and plays a key role in the initial steps of the whole process of reverse cholesterol transport (RCT). Upregulation of ABCA1 is beneficial for atherosclerosis (AS) prevention and/or therapy, which indicated that ABCA1 was a target for anti-AS drug development. In the previous study, a high-throughput screening method was established using ABCA1p-LUC HepG2 cell line to find the upregulators of ABCA1. In the present study, compound 2030421B was found using this method, with EC50 of 0.50 microg x mL(-1). The compound was further identified as an upregulator of ABCA1 expression by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting analysis. Studies also showed that the 2030421B could induce apoA-I-mediated cholesterol efflux and inhibit lipids uptake into mouse peritoneal macrophages RAW264.7.
ATP Binding Cassette Transporter 1 ; ATP-Binding Cassette Transporters ; genetics ; metabolism ; Animals ; Anticholesteremic Agents ; administration & dosage ; chemistry ; pharmacology ; Apolipoprotein A-I ; metabolism ; Benzaldehydes ; administration & dosage ; chemistry ; pharmacology ; Biological Transport ; Cells, Cultured ; Cholesterol ; secretion ; Dose-Response Relationship, Drug ; Hep G2 Cells ; High-Throughput Screening Assays ; Humans ; Lipid Metabolism ; Lipids ; analysis ; Macrophages, Peritoneal ; cytology ; metabolism ; Mice ; Molecular Structure ; RNA, Messenger ; Up-Regulation ; drug effects

OBJECTIVETo screen and identify differential serum proteins which might be involved in dermatitis medicamentosa-like of trichloroethylene (DMLT).

METHODSThree groups of sera were collected from population exposed to trichloroethylene (TCE) (group I), patients suffering from DMLT (group II), and the healed cases (group III). After removing albumin and IgG in the three pools of sera, a comparative proteomic analysis was carried out. The images were analyzed using ImageMaster Platinum 2D 5.0 to screen the differentially expressed proteins. The protein spots were then subjected to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and tandem mass spectrometry sequencing of tryptic peptides for further identification.

RESULTSThe depletion of albumin and IgG greatly increased the number of protein spots to 300 ± 12.Five differential spots were identified, which were complement component C4b, apolipoprotein A-I, apolipoprotein C-III apolipoprotein C-II and transthyretin. Compared with group I, the expression levels of complement component C4b in group III and apolipoprotein C-II in group II were up-regulated (1.352 88-fold, 1.512 14-fold, respectively); compared with group I, the expression levels of apolipoprotein A-I, apolipoprotein C-III and transthyretin in group II were down-regulated (1.601 17-fold, 1.034 49-fold, 1.313 35-fold, respectively).

CONCLUSIONThe findings of this study show that most of the identified differential proteins are closely related to immunity and liver dysfunction, which provides some evidence on elucidating the mechanisms and screening of biomarkers of TCE intoxication.

Adolescent ; Adult ; Apolipoprotein A-I ; isolation & purification ; Apolipoprotein C-III ; isolation & purification ; Biomarkers ; analysis ; Blood Proteins ; chemistry ; isolation & purification ; Dermatitis, Occupational ; blood ; Drug Eruptions ; blood ; Environmental Exposure ; Female ; Humans ; Male ; Proteome ; analysis ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Trichloroethylene ; adverse effects ; Young Adult

BACKGROUNDHigh-density lipoprotein cholesterol (HDL-C) levels are a strong, independent inverse predictor of coronary heart disease (CHD). In this cross-sectional study we investigated the interrelationships between HDL-C and HDL related factors apolipoprotein A-I (apoA-I) and serum amyloid A (SAA) and the presence and extent of CHD in a population of Chinese patients with CHD.

METHODSTwo hundred and twenty-four consecutive patients took part in this study. Demographic data were obtained from hospital records. Serum chemical concentrations were measured by standard laboratory methods.

RESULTSThe concentrations of high-sensitive C-reactive protein (hsCRP) (median: 1.85 mg/L) and SAA (median: 9.40 mg/L) were significantly higher in the CHD group (P < 0.05), while concentrations of HDL-C ((1.03 +/- 0.25) mmol/L) and apoA-I ((604.59 +/- 105.79) mmol/L) were significantly lower than those in the non-CHD group (P < 0.05). The concentrations of apoA-I decreased with the increase in vascular damage, but the difference did not reach statistical significance. However, the concentrations of hsCRP and SAA increased with the increase in vascular damage. The unadjusted odd ratios (ORs) (CI) for apoA-I and SAA of the presence of CHD were 0.093 (0.990 - 0.997) (P = 0.00) and 2.571 (1.029 - 6.424) (P < 0.05), respectively. The association between elevated SAA and the presence of CHD was lost after adjusting for lipid status parameter concentrations. The associations between apoA-I, SAA and the extent of CHD remained strong, regardless of confounding variables.

CONCLUSIONSIncreased concentrations of SAA represent the inflammatory marker of the extent of coronary stenosis in patients with CHD. In contrast to SAA, the level of apoA-I was also associated with the presence of CHD, indicating that apoA-I was not only a marker of CHD presence but also a quantitative indicator of CHD extent. In short, determining the change apolipoprotein content within HDL particle is a more accurate and effective method to evaluate the impact of HDL on CHD.

Adult ; Aged ; Apolipoprotein A-I ; blood ; Biomarkers ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Coronary Disease ; blood ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Serum Amyloid A Protein ; analysis

BACKGROUND/AIMS: The elasticity of the aorta modulates the entire cardiovascular system. Increasing arterial stiffness with the loss of aortic elasticity is not only a surrogate marker for early atherosclerosis, but also a predictor of cardiovascular events. METHODS: This study included 203 patients (57.6+/-14.7 years, 117 male) who underwent diagnostic transesophageal echocardiography. We investigated the correlation between the arterial stiffness index (beta stiffness index), which is calculated from the distensibility of the descending thoracic aorta and blood pressure, and known serologic markers of atherosclerosis and cardiovascular events. RESULTS: The beta stiffness index correlated significantly with the brachial-ankle pulse wave velocity (R2=0.243, p<0.001) and intima-media thickness of the descending thoracic aorta (R2= 0.470, p<0.001). It also correlated with age (r=0.465, p<0.001) and the presence of diabetes mellitus (r=0.250, p<0.001). The beta stiffness index was significantly positively correlated with the levels of N-terminal pro-brain natriuretic peptide (NT- proBNP), high-sensitivity C-reactive protein (hsCRP), glucose, HbA1c, apolipoprotein (Apo) A-I, and erythrocyte sediment rate. A multivariate regression analysis demonstrated that the beta stiffness index was associated with the levels of NT-proBNP, hsCRP, HbA1c, and Apo A-I. CONCLUSIONS:The beta stiffness index for the distensibility of the descending thoracic aorta significantly correlates with other parameters of arterial stiffness and serologic markers for atherosclerosis. Therefore, the beta stiffness index can be used as a parameter of cardiovascular events in diseases requiring transesophageal echocardiography, such as atrial fibrillation and mitral stenosis.
Aorta ; Aorta, Thoracic ; Apolipoprotein A-I ; Apolipoproteins ; Atherosclerosis ; Atrial Fibrillation ; Biomarkers ; Blood Pressure ; C-Reactive Protein ; Cardiovascular System ; Diabetes Mellitus ; Echocardiography ; Echocardiography, Transesophageal ; Elasticity ; Erythrocytes ; Glucose ; Humans ; Mitral Valve Stenosis ; Natriuretic Peptide, Brain ; Peptide Fragments ; Pulse Wave Analysis ; Vascular Stiffness

OBJECTIVETo detect and identify the potential specific serum biomarkers for diagnosis of papillary thyroid cancer.

METHODSSamples of 35 patients with papillary thyroid carcinoma, 40 patients with benign thyroid nodule and 34 healthy individuals were analyzed using the SELDI-TOF ProteinChip System and bioinfomation technology to find the differential peaks which were separated by HPLC and then further analyzed by LC-MS/MS. The protein sequences were analyzed by SEQUEST software and searched in Bioworks database.

RESULTSThe top six mass-to-charge ratio (M/Z) peaks with the smallest P value were 6651, 6452, 7653, 7932, 15 106 and 15 848 Da, respectively. The 6651 and 6452 Da proteins were weakly expressed in papillary thyroid carcinoma but highly expressed in benign thyroid nodules and healthy individuals. The differences had statistical significance (P < 0.01). The 7653, 7932, 15 106, 15 848 Da proteins were highly expressed in papillary thyroid carcinoma but weakly expressed in benign thyroid nodules and healthy individuals. The differences were statistically significant (P < 0.01). Combination of these six proteins, using the method of leave-one-out to make crossing detection, the specificity of discriminating papillary thyroid carcinoma and non-cancer was 88.0%, and its sensitivity was 92.5%. The 6651 and 6452 Da proteins were identified as apolipoprotein C-I and apolipoprotein C-III, respectively. The 7653 and 15 106 Da proteins were identified as the same protein-alpha-globin, and the 7932 and 15,848 Da proteins were identified as the same protein-beta-globin.

CONCLUSIONThe detection of differentially expressed apolipoprotein C-I, apolipoprotein C-III, alpha-globin, and beta-globin may have utility for diagnosis of papillary thyroid carcinoma and are worthy of further investigation.

Adult ; Apolipoprotein C-I ; blood ; Apolipoprotein C-III ; blood ; Biomarkers, Tumor ; blood ; Carcinoma, Papillary ; blood ; diagnosis ; Female ; Humans ; Male ; Middle Aged ; Protein Array Analysis ; Proteomics ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Thyroid Neoplasms ; blood ; diagnosis ; alpha-Globins ; metabolism ; beta-Globins ; metabolism