Although elevated serum low-density lipoprotein-cholesterol (LDL-C) is without any doubts accepted as an important risk factor for cardiovascular disease (CVD), the role of elevated triglycerides (TGs)-rich lipoproteins as an independent risk factor has until recently been quite controversial. Recent data strongly suggest that elevated TG-rich lipoproteins are an independent risk factor for CVD and that therapeutic targeting of them could possibly provide further benefit in reducing CVD morbidity, events and mortality, apart from LDL-C lowering. Today elevated TGs are treated with lifestyle interventions, and with fibrates which could be combined with omega-3 fatty acids. There are also some new drugs. Volanesorsen, is an antisense oligonucleotid that inhibits the production of the Apo C-III which is crucial in regulating TGs metabolism because it inhibits lipoprotein lipase (LPL) and hepatic lipase activity but also hepatic uptake of TGs-rich particles. Evinacumab is a monoclonal antibody against angiopoietin-like protein 3 (ANGPTL3) and it seems that it can substantially lower elevated TGs levels because ANGPTL3 also regulates TGs metabolism. Pemafibrate is a selective peroxisome proliferator-activated receptor alpha modulator which also decreases TGs, and improves other lipid parameters. It seems that it also has some other possible antiatherogenic effects. Alipogene tiparvovec is a nonreplicating adeno-associated viral vector that delivers copies of the LPL gene to muscle tissue which accelerates the clearance of TG-rich lipoproteins thus decreasing extremely high TGs levels. Pradigastat is a novel diacylglycerol acyltransferase 1 inhibitor which substantially reduces extremely high TGs levels and appears to be promising in treatment of the rare familial chylomicronemia syndrome.
Apolipoprotein C-III ; Cardiovascular Diseases ; Diacylglycerol O-Acyltransferase ; Fatty Acids, Omega-3 ; Fibric Acids ; Hyperlipoproteinemia Type I ; Life Style ; Lipase ; Lipoprotein Lipase ; Lipoproteins ; Metabolism ; Mortality ; PPAR alpha ; Risk Factors ; Triglycerides

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

PURPOSE: 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

BACKGROUND AND OBJECTIVES: The relationship between short-term hypothyroidism due to levothyroxine (LT4) withdrawal for radioactive iodine (RI) therapy in patients with differentiated thyroid cancer (DTC) and risk of cardiovascular disease is not clear. In this study, we evaluated the impact of short-term overt hypothyroidism on lipid profiles and cardiovascular parameters in patients with DTC. MATERIALS AND METHODS: We recruited 195 patients with DTC who were preparing RI therapy from March 2008 to February 2012. We analyzed the effect of thyroid stimulating hormone (TSH) level on the clinical, biochemical, and cardiovascular risk markers at the end of LT4 withdrawal protocol (P2). RESULTS: After LT4 withdrawal (P2), TSH and total cholesterol (TC) levels were significantly increased (p<0.005). After adjustment for multiple factors such as age, sex, body mass index (BMI), hypertension and diabetes mellitus (DM), the positive relationship between TSH and TC remained significant (p=0.04). Mean levels of homocysteine, low density lipoprotein-cholesterol, triglyceride were increased. However, levels of high density lipoprotein-cholesterol, cystatin C, C-reactive protein, apolipoprotein B (ApoB), apolipoprotein A1 (Apo A1), lipoprotein (a) (Lp[a]), aspartate transaminase, alanine aminotransferase, total bilirubin, uric acid remained within normal range. Splitting the whole cohort into the three different age groups, serum Apo B, Lp(a) levels and BMI increased with increasing age (p<0.05). And splitting into three different TSH level groups (1st group; <79 microIU/mL, 2nd group; 79-121 microIU/mL, 3rd group; >121 microIU/mL), all values did not have a statistical significant meaning except Apo A1. CONCLUSION: Short-term hypothyroidism induced worsening of lipid metabolic parameters, but not enough to induce the cardiovascular risk in patients with thyroid cancer.
Alanine Transaminase ; Apolipoprotein A-I ; Apolipoproteins ; Apolipoproteins B ; Aspartate Aminotransferases ; Bilirubin ; Body Mass Index ; C-Reactive Protein ; Cardiovascular Diseases ; Cholesterol ; Cohort Studies ; Cystatin C ; Diabetes Mellitus ; Homocysteine ; Humans ; Hypertension ; Hypothyroidism ; Iodine* ; Lipoprotein(a) ; Reference Values ; Thyroid Neoplasms ; Thyrotropin ; Thyroxine ; Triglycerides ; Uric Acid

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.
Adult ; Apolipoprotein A-I ; Apolipoprotein A-II ; Apolipoproteins ; Apolipoproteins B ; Asian Continental Ancestry Group ; C-Reactive Protein ; Health Promotion ; Homocysteine ; Humans ; Lipoproteins ; Prevalence

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

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

Androgens play a central role in prostate cancer pathogenesis, and hence most of the patients respond to androgen deprivation therapies. However, patients tend to relapse with aggressive prostate cancer, which has been termed as hormone refractory. To identify the proteins that mediate progression to the hormone-refractory state, we used protein-chip technology for mass profiling of patients' sera. This study included 16 patients with metastatic hormone-refractory prostate cancer who were initially treated with androgen deprivation therapy. Serum samples were collected from each patient at five time points: point A, pre-treatment; point B, at the nadir of the prostate-specific antigen (PSA) level; point C, PSA failure; point D, the early hormone-refractory phase; and point E, the late hormone-refractory phase. Using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, we performed protein mass profiling of the patients' sera and identified a 6 640-Da peak that increased with disease progression. Target proteins were partially purified, and by amino acid sequencing the peak was identified as a fragment of apolipoprotein C-I (ApoC-I). Serum ApoC-I protein levels increased with disease progression. On immunohistochemical analysis, the ApoC-I protein was found localized to the cytoplasm of the hormone-refractory cancer cells. In this study, we showed an increase in serum ApoC-I protein levels in prostate cancer patients during their progression to the hormone-refractory state, which suggests that ApoC-I protein is related to progression of prostate cancer. However, as the exact role of ApoC-I in prostate cancer pathogenesis is unclear, further research is required.
Aged ; Amino Acid Sequence ; Antineoplastic Agents, Hormonal ; therapeutic use ; Apolipoprotein C-I ; analysis ; blood ; isolation & purification ; Blotting, Western ; Cell Line ; Disease Progression ; Drug Resistance, Neoplasm ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Molecular Sequence Data ; Prognosis ; Prostatic Neoplasms ; drug therapy ; metabolism ; Protein Array Analysis ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

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

BACKGROUND: The incidence of type 2 diabetes mellitus is increasing annually and patient mortality is high. Coronary artery calcification is a predictor of coronary artery disease. Cardiovascular events, which are the main cause of death in type 2 diabetes patients, may be preventable by addressing risk factors associated with coronary artery calcification. We examined the relationships between coronary artery calcification, lipid profiles, and apolipoprotein levels. METHODS: We calculated the coronary calcium scores (CCS) of 254 subjects with type 2 diabetes (113 males, 141 females) via multi-detector row computed tomography (MDCT). Height, body weight, blood pressure, HbA1c, c-peptide, lipid profile and apolipoprotein were assessed concurrently. RESULTS: In patients with type 2 diabetes, Agatston score and apolipoprotein A-1 were significantly negatively correlated in both males and females (males P = 0.015, females P = 0.021). The negative correlation between Agatston score and apolipoprotein A-1 was retained for the entire patient sample after adjustments for age and sex (P = 0.022). Stepwise multiple regression anaylses with the Agatston score as the dependent variable indicate that apolipoprotein A-1 is a independent predictor (beta coefficient = -0.047, 95%CI = -0.072 ~ -0.021, P < 0.001) of coronary artery calcification. CONCLUSION: The results of our study suggest that apolipoprotein A-1 is a useful independent indicator of coronary artery calcification.
Apolipoprotein A-I ; Apolipoproteins ; Atherosclerosis ; Blood Pressure ; Body Height ; C-Peptide ; Calcium ; Cardiovascular Diseases ; Cause of Death ; Coronary Artery Disease ; Coronary Vessels ; Diabetes Mellitus, Type 2 ; Female ; Humans ; Incidence ; Male ; Risk Factors