Anita Szentpéteri

Alteration of the irisin–brain-derived neurotrophic factor axis contributes to disturbance of mood in COPD patients

COPD is accompanied by limited physical activity, worse quality of life, and increased prevalence of depression. A possible link between COPD and depression may be irisin, a myokine, expression of which in the skeletal muscle and brain positively correlates with physical activity. Irisin enhances the synthesis of brain-derived neurotrophic factor (BDNF), a neurotrophin involved in reward-related processes. Thus, we hypothesized that mood disturbances accompanying COPD are reflected by the changes in the irisin–BDNF axis. Case history, routine laboratory parameters, serum irisin and BDNF levels, pulmonary function, and disease-specific quality of life, measured by St George’s Respiratory Questionnaire (SGRQ), were determined in a cohort of COPD patients (n=74). Simple and then multiple linear regression were used to evaluate the data. We found that mood disturbances are associated with lower serum irisin levels (SGRQ’s Impacts score and reciprocal of irisin showed a strong positive association; β: 419.97; 95% confidence interval [CI]: 204.31, 635.63; P<0.001). This association was even stronger among patients in the lower 50% of BDNF levels (β: 434.11; 95% CI: 166.17, 702.05; P=0.002), while it became weaker for patients in the higher 50% of BDNF concentrations (β: 373.49; 95% CI: −74.91, 821.88; P=0.1). These results suggest that irisin exerts beneficial effect on mood in COPD patients, possibly by inducing the expression of BDNF in brain areas associated with reward-related processes involved in by depression. Future interventional studies targeting the irisin–BDNF axis (eg, endurance training) are needed to further support this notion.

Serum obestatin level strongly correlates with lipoprotein subfractions in non-diabetic obese patients

BackgroundObestatin is a ghrelin-associated peptide, derived from preproghrelin. Although many of its effects are unclear, accumulating evidence supports positive actions on both metabolism and cardiovascular function. To date, level of obestatin and its correlations to the lipid subfractions in non-diabetic obese (NDO) patients have not been investigated.MethodsFifty NDO patients (BMI: 41.96u2009±u20098.6xa0kg/m2) and thirty-two normal-weight, age- and gender-matched healthy controls (BMI: 24.16u2009±u20093.3xa0kg/m2) were enrolled into our study. Obestatin level was measured by ELISA. Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions, intermediate density lipoprotein (IDL) and very low-density lipoprotein (VLDL) levels and mean LDL size were detected by nongradient polyacrylamide gel electrophoresis (Lipoprint).ResultsSerum level of obestatin was significantly lower in NDO patients compared to controls (3.01xa0±u20090.5 vs. 3.29u2009±u20090.6xa0μg/ml, pu2009<u20090.05). We found significant negative correlations between the level of obestatin and BMI (ru2009=u2009−u20090.33; pu2009<u20090.001), level of serum glucose (ru2009=u2009−u20090.27, pu2009<u20090.05), HbA1c (ru2009=u2009−u20090.38; pu2009<u20090.001) and insulin (ru2009=u2009−u20090.34; pu2009<u20090.05). Significant positive correlation was found between obestatin level and the levels of ApoA1 (ru2009=u20090.25; pu2009<u20090.05), large HDL subfraction ratio and level (ru2009=u20090.23; pu2009<u20090.05 and ru2009=u20090.24; pu2009<u20090.05), IDL (ru2009=u20090.25 pu2009<u20090.05) and mean LDL size (ru2009=u20090.25; pu2009<u20090.05). Serum VLDL ratio and level negatively correlated with obestatin (ru2009=u2009−u20090.32; pu2009<u20090.01 and ru2009=u2009−u20090.21; pu2009=u20090.05). In multiple regression analysis obestatin was predicted only by VLDL level.ConclusionsBased on our data, measurement of obestatin level in obesity may contribute to understand the interplay between gastrointestinal hormone secretion and metabolic alterations in obesity.

Paraoxonase-1 arylesterase activity is an independent predictor of myeloperoxidase levels in overweight patients with or without cardiovascular complications.

OBJECTIVESnMyeloperoxidase (MPO), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were shown to contribute to atherogenesis, while human paraoxonase-1 (PON1) protects against oxidative stress. Although several studies investigated these biomarkers, their associations have not been completely clarified yet. We aimed to investigate these parameters in overweight hyperlipidemic, lipid-lowering therapy-naive patients (n=167) with and without vascular complications.nnnDESIGN AND METHODSnMPO, MMP-9 and TIMP-1 levels were measured by ELISA. PON1 activities were detected spectrophotometrically. PON1 phenotype was calculated by using a dual substrate method.nnnRESULTSnPatients with vascular complications (VC) had significantly higher MPO and TIMP-1 levels compared to those without (patients with no vascular complications; NVC) (728 (367.25-1177.90) mg/ml vs. 315.9 (176.05-687.40) mg/ml; p<0.001; and 172.7 (157.7-197.7) ng/ml vs. 152.6 (129.3-172.3) ng/ml; p<0.0001; respectively). MPO levels showed a significant negative correlation with PON1 arylesterase activity (whole patient group (W): r=0.42, p<0.0001; VC: r=0.44, p=0.01; NVC: r=0.39, p<0.0001) and positive correlations with MMP-9 (W: r=0.37, p<0.0001; VC: r=0.29, p=0.07; NVC: r=0.42, p<0.0001) and TIMP-1 (W: r=0.42, p<0.0001; VC: r=0.33, p<0.05; NVC: r=0.41, p<0.0001), respectively. PON1 arylesterase activity was found to be an independent predictor of MPO levels in the whole patient group (β=-0.350, p<0.0001) or when studied separately in the subgroups with or without cardiovascular complications (VC: β=-0.57, p<0.05; NVC: β=-0.33, p<0.0001).nnnCONCLUSIONSnOur results suggest that parallel investigation of MPO, MMP-9 and TIMP-1 levels and PON1 arylesterase activity may be a more accurate indicator of atherosclerosis, which may allow earlier treatment and therefore, improvement of treatment efficacy.

Az apolipoprotein M és a szfingozin-1-foszfát tengely jelentősége az érelmeszesedés kialakulásának gátlásában

Absztrakt: Korabbi tanulmanyok igazoltak, hogy a plazma high-density lipoprotein (HDL)-szintje forditottan aranyos a sziv- es errendszeri betegsegek kialakulasanak kockazataval. Az utobbi evtizedekben azonban nyilvanvalova valt, hogy a HDL szerkezete es műkodese kulcsfontossagu az erelmeszesedest gatlo hatas kialakulasaban. Az apolipoprotein M (ApoM) egy HDL-hez kotott plazmafeherje, mely befolyasolja a HDL metabolizmusat es szamos, erelmeszesedest gatlo hatassal rendelkezik, peldaul ved az oxidacioval szemben es szabalyozza a sejtek koleszterinleadasat. A szfingozin-1-foszfat (S1P) egy hatekony szfingolipidkozvetitő molekula, mely a sejtek kulonboző funkcioit szabalyozza, beleertve a sejtek differenciaciojat es migraciojat, a programozott sejthalalt es az erfali gyulladast. Az S1P főkent az ApoM-et tartalmazo HDL-reszecskekhez kototten kering. Mindezek alapjan a HDL ApoM- es S1P-tartalma kihat az erelmeszesedes folyamatara. Raadasul a HDL ApoM- es S1P-tartalma modosulhat kulonboző korallapotokban, peldau...Previous studies showed that plasma levels of high-density lipoprotein (HDL) cholesterol are inversely related to risk of cardiovascular diseases. However, in the last few decades it became obvious that beyond its plasma level, HDL structure and function have a critical role in its anti-atherogenic efficacy. Apolipoprotein M (ApoM) is an HDL-associated plasma protein affecting HDL metabolism and exhibits various anti-atherosclerotic functions, such as protection against oxidation and regulation of cholesterol efflux. Sphingosine 1-phosphate (S1P) is a potent sphingolipid mediator that regulates numerous cellular responses including cell differentiation and migration, apoptosis and vascular inflammation. The majority of S1P is associated to ApoM containing HDL particles. Therefore, ApoM and S1P content of HDL have an impact on the atherosclerotic process. Moreover, HDL-ApoM and S1P content can be altered in several pathologic conditions such as coronary artery disease. This review covers the currently available data on the contribution of ApoM and S1P to HDL function in health and cardiovascular diseases. Orv Hetil. 2018; 159(5): 168-175.

Changes in serum afamin and vitamin E levels after selective LDL apheresis: VARGA et al.

Afamin is a plasma vitamin E‐binding glycoprotein partially associated with ApoA1‐containing high‐density lipoprotein (HDL) subfractions. In a previous study, the serum vitamin E decreased after low‐density lipoprotein (LDL) apheresis, while vitamin E/cholesterol ratio increased. We aimed to study the effect of LDL apheresis on serum afamin level.

HDL subfraction distribution and HDL function in untreated dyslipidemic patients

Aim: The protective role of high-density lipoprotein (HDL) against atherosclerosis is well known. However, both structural and functional changes of the HDL particles may affect its protective efficacy. Increased levels of HDL-associated myeloperoxidase (MPO) and decreased HDL-linked paraoxonase-1 (PON1) activity have been reported in dyslipidemic patients. Some changes in HDL subfraction distributions were also studied previously, but data on structural and functional changes in dyslipidemia are not complete. Therefore, the authors aimed to evaluate these qualitative and quantitative markers of HDL in dyslipidemic patients and healthy control subjects. Methods: Anthropometric parameters, serum levels of lipoproteins and MPO, as well as PON1 activities were investigated in 81 untreated dyslipidemic patients and in 32 healthy gender-matched controls. Additionally, HDL subfractions were detected by an electrophoretic method on polyacrylamide gel (Lipoprint). Results: Significantly higher glucose, hemoglobin A1c, total cholesterol, low-density lipoprotein-cholesterol, triglyceride, lipoprotein(a), apolipoprotein B, C-reactive protein, and MPO levels were found in patients compared to the healthy subjects. There were no significant differences in PON1 paraoxonase and arylesterase activities between the two study groups, but MPO/PON1 ratio was significantly higher in patients. There was a shift towards the smaller HDL subfractions, but only the intermediate HDL ratio was significantly lower in patients compared to controls. Conclusion: The results highlight the importance of HDL-associated proand antioxidant enzymes suggesting the possible clinical benefit of MPO/PON1 calculation and confirm that quantification of HDL-C level alone provides limited data regarding HDL’s cardioprotective effect. Calculation of MPO/PON1 ratio may be a useful cardiovascular marker in dyslipidemia.

Paraoxonase-1 and myeloperoxidase correlate with vascular biomarkers in overweight patients with newly diagnosed untreated hyperlipidaemia

BACKGROUNDnIn hyperlipidaemic state, increased levels of myeloperoxidase (MPO) and decreased paraoxonase-1 (PON1) activity have been reported; however, their relationships with other atherosclerotic biomarkers have not been completely clarified.nnnPATIENTS AND METHODSnSerum concentrations of lipid and inflammatory parameters, MPO levels, and PON1 activities were investigated in 167 untreated hyperlipidaemic patients with and without vascular complications and in 32 healthy controls. Additionally, levels of CD40 ligand (sCD40L) and asymmetric dimethyl arginine (ADMA), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1, and oxidized LDL were determined.nnnRESULTSnWe found elevated C-reactive protein (CRP), ADMA, sCD40L, sICAM-1 concentrations, and higher MPO levels in patients with vascular complications compared to those without. The PON1 arylesterase activity correlated negatively with sCD40L, ADMA, and sICAM-1 levels, respectively. In contrast, MPO concentrations showed positive correlations with sCD40L, ADMA, and sICAM-1 levels, respectively.nnnCONCLUSIONSnIt can therefore be stated that PON1 activity and MPO level correlate strongly with the vascular biomarkers, highlighting the importance of the HDL-associated pro- and antioxidant enzymes in the development of endothelial dysfunction and atherogenesis.

Serum afamin concentration positively correlates with the levels of pro-inflammatory adipokines in obesity

s / Atherosclerosis 263 (2017) e111ee282 e200 Chew-Kiat Heng, Delicia Shuqin Ooi, Rajkumar Dorajoo, Mark YanYee Chan, Adrian Fatt-Hoe Low, Yechiel Friedlander. Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Khoo Teck Puat National University Childrens Medical Institute, National University Hospital, Singapore, Singapore; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; National University Heart Centre, National University Hospital, Singapore, Singapore; 6 School of Public Health and Community Medicine, Hebrew University of Jerusalem, Jerusalem, Israel Aim: ADTRP is a recently identified protein that may be involved in the pathogenesis of coronary artery disease (CAD). However, very little is known about its role. We carried out several preliminary investigations in this study. Methods: We used Human Coronary Artery Endothelial Cells (HCAEC) for in vitro investigations and measured circulating levels of ADTRP in blood samples of CAD patients and controls by ELISA. RNA transcripts were estimated using quantitative real-time PCR. Results: We were able to detect the presence of both ADTRP and Tissue Factor Pathway Inhibitor (TFPI) RNA transcripts in HCAEC and human blood samples. Three androgen response elements were identified in silico by the PROMO algorithm at ~180bp, ~ 200bp and ~1500bp upstream of the start codon of the ADTRP gene. These sites showed a dissimilarity of 5.25%, 5.64% and 6.46% respectively compared to the consensus site for androgen receptor. Treatment of HCAEC with 0, 30, 50nM of dihydrotestosterone for 24 hours led to a dose-dependent increase in ADTRP and TFPI transcripts. We measured plasma ADTRP and found significantly lower levels in CAD patients (1.44 ± 0.99pg/ml) compared to control subjects (22.73± 12.93pg/ ml). Conclusions: ADTRP expressionwas increased by androgen treatment in a dose-dependent manner. This possibly led to a corresponding increase in the expression of its target protein, TFPI. We have also shown for the first time that ADTRP is detectable in circulation and that CAD patients have significantly lowered plasma levels compared to healthy subjects. Thus ADTRP may potentially serve as a novel biomarker for CAD. PO291. SERUM AFAMIN CONCENTRATION POSITIVELY CORRELATES WITH THE LEVELS OF PRO-INFLAMMATORY ADIPOKINES IN OBESITY Ildiko Seres, Hajnalka Lorincz, Viktoria E. Varga, Anita Szentpeteri, Sandor Somodi, Mariann Harangi, Peter Fulop, Gyorgy Paragh. Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary Aim: Human afamin has been shown to be a specific binding protein for aand g-tocopherols, two of the most important forms of vitamin E. This glycoprotein is predominantly expressed in the liver and secreted into the circulation. Elevated afamin level is found to be strongly associated with the components of metabolic syndrome including visceral obesity. Visceral adipose tissue is considered an active endocrine organ secreting biologically active proteins termed adipokines. Previously, correlations between the levels afamin and proor anti-inflammatory adipokines have not been studied. Methods: We enrolled fifty obese (BMI: 41.96±8.6 kg/m2) and thirty-two gender and age-matched lean (BMI: 24.2±2.5 kg/m2) subjects without manifest carbohydrate and lipid disturbances. Serum levels of afamin, leptin, interleukin-6 (IL-6), retinol binding protein-4 (RBP-4), pigment epithelium derived factor (PEDF), plasminogen activator inhibitor-1 (PAI1), adiponectin and omentin-1 were measured by ELISA. Results: Circulating afamin concentration was significantly higher in the obese group (70.4±12.9 mg/ml) compared to controls (47.6±8.5 mg/ ml; p<0.0001). In overall subjects, strong positive correlations were observed between serum afamin and leptin (r1⁄40.40; p<0.001), IL-6 (r1⁄40.60; p<0.001) RBP-4 (r1⁄40.24; p<0.05), PEDF (r1⁄40.56; p<0.001) and PAI-1 (r1⁄40.48; p<0.001) levels. Anti-inflammatory adiponectin and omentin-1 levels did not show association with afamin concentration. Conclusions: Strong correlations with pro-inflammatory adipokines may highlight the key role of afamin in metabolic syndrome and obesity. PO292. A NEW METHOD TO DETERMINE THE MODIFIED LDL ATHEROGENICITY AMONG PATIENTS AT LOW CARDIOVASCULAR RISK Sofia Eliashevich, Oxana Drapkina, Batogab Shoibonov. National Research Center for Preventive Medicine, Moscow, Russia Aim: To determine the diagnostic value of the lytic activity test of multiply modified LDL in patients at low cardiovascular risk. Methods: A pilot study, including 41 patients without evidence of atherosclerosis (IMT < 0,9 mm) at low CVD risk according to SCORE, was designed. Abdominal obesity was detected according to the IDF criteria (2009). The lytic activity test of multiply modified LDL (%) was assessed by using original techniques. Results: Analysis included 41 participants (mean age: 41 (9) years; body mass index: 27 (5) kg/m2; and 46% male). Mean lipid values were as follows: total cholesterol: 5.5 (1) mmol/l; LDL-C: 3.7 (0,9) mmol/l; HDLC: 0.99 (0.3) mmol/l; TG 2.5 (1.5 e 2.1) mmol/l. 23 (56%) participants of the sample had signs of abdominal obesity. The lytic activity test showed the high level of autologous red blood cells lysis by mLDL, which indicates the high mLDL atherogenicity, regardless of the waist circumference. There were found nonsignificant differences in the mLDL lytic activity in patients with abdominal obesity and without it: 100% (95 e 100) vs 74% (36 e 95), accordingly (p> 0,05). Normally the allowable values of the mLDL lytic activity in patients with low atherogenic mLDL is up to 10%. The mLDL lytic activity was associated with hs-CRP (r1⁄40.4, p<0.05), independently of LDL-C and other variables. Conclusions: The identification the mLDL lytic activity against own red blood cells indicates a high pathogenicity of mLDL and opens a qualitatively new approach to the evaluation of atherogenicity as opposed to quantify lipoproteins fractions. PO293. COMPLEMENT C3 AS A PREDICTOR FOR METABOLIC SYNDROME IN MORBID OBESITY Stefanie Van Mil, Ulas Biter, Gert-Jan Van De Geijn, Guido Mannaerts, Manuel Castro Cabezas. 1 Franciscus Gasthuis, Department of Surgery, Rotterdam, The Netherlands; 2 Franciscus Gasthuis, Department of Clinical Chemistry, Rotterdam, The Netherlands; 3 Tawam Hospital, Department of Surgery, Al Ain, United Arab Emirates; 4 Franciscus Gasthuis, Department of Internal Medicine, Rotterdam, The Netherlands Aim: Complement C3 (C3) is best known for its role in the immune system, although C3 levels are also associated with cardiovascular risk factors, type 2 diabetes mellitus, familial combined hyperlipidemia and the metabolic syndrome. We hypothesized that C3 is a predictor of metabolic syndrome (MetS) in subjects suffering from morbid obesity. Methods: Morbidly obese subjects scheduled for bariatric surgery between 2007 and 2013 in our hospital were included. Baseline characteristics and laboratory values were collected. Differences between subjects with and without MetS were tested using chi-squared tests and independent T-tests. Correlations were expressed in Spearman’s correlation coefficients. Odds ratios (OR) of MetS were obtained using logistic regression analysis. Results: A total of 1046 morbidly obese subjects were included (81.8% women), mean age of 42.9±10.8 years. MetS was diagnosed in 731 subjects (69.9%). The group of MetS included significantly more men (21.2% and 11.1%, respectively) and were older (44.6±10.4 and 39.1±10.8 years,