Reverse modulation of the HDL Anionic Peptide Factor and phospholipid transfer protein activity in coronary artery disease and type 2 diabetes mellitus

ObjectivesThe high density lipoprotein Anionic Peptide Factor (HDL₃-APF) was previously described as an apolipoprotein that promotes the reverse cholesterol transport. Since phospholipid transfer protein (PLTP) is involved in such mechanism we attempted to focus on the two APF and PLTP proteins.Design and methodsWe recruited 56 type 2 diabetic patients with (n = 36) or without (n = 20) coronary artery disease (CAD) and 19 CAD patients. The three groups were compared to 39 healthy control subjects. In all groups, lipid profile was determined and plasma APF concentrations and PLTP activity were measured.ResultsIn all patients, the PLTP activity was significantly increased in comparison with controls (p < 0.01), in concomitance with a plasma APF level decrease in groups with CAD (with and without type 2 diabetes) (p < 0.01). Multiple linear regression analysis demonstrated that, when apoA-I, HDL-C, HDL-phospholipids and PLTP activity were taken into account as independent variables (after univariate regression analysis), HDL-PL was positively and independently related to APF (p < 0.0001 in whole population; p = 0.0090 in controls) and PLTP activity was negatively and independently related to APF in whole population and all patients' groups (all p < 0.05), but positively and independently associated to APF in controls (p = 0.0005).ConclusionsAPF could be considered as a specific marker against CAD and type 2 diabetes mellitus and our results confirm the atherogenic behavior of PLTP in CAD. Thus, these two proteins are likely to be regulated in a reverse manner.     

Increased large VLDL and small LDL particles are related to lower bilirubin in Type 2 diabetes mellitus

ObjectivesBilirubin may protect against atherosclerotic cardiovascular disease by virtue of its anti-oxidative properties, but lower bilirubin may also be associated to atherogenic lipoprotein abnormalities. We determined associations of plasma (apo)lipoproteins and lipoprotein subfractions in subjects with and without type 2 diabetes mellitus (T2DM).Design and methodsPlasma (apo)lipoproteins, lipoprotein subfractions (nuclear magnetic resonance spectroscopy) and serum total bilirubin levels were determined in 53 T2DM patients and in 53 non-diabetic subjects.ResultsTriglycerides, large VLDL, small LDL and small HDL particles were increased (all p < 0.05), whereas HDL cholesterol, apoA-I and large HDL particles were decreased (all p < 0.05), coinciding lower bilirubin levels in T2DM (p < 0.001). In age- and sex-adjusted analysis, total cholesterol, non-HDL cholesterol, triglycerides, apoB, apoE, large VLDL and small LDL were negatively correlated with bilirubin, but HDL cholesterol was positively correlated with bilirubin in T2DM (p < 0.05 to p < 0.001). Multivariable linear regression analyses demonstrated that in all subjects combined total cholesterol, non-HDL cholesterol, triglycerides and apoE were negatively associated with bilirubin after adjustment for age, sex, T2DM, body mass index and alanine aminotransferase (all p < 0.05). Further multivariable linear regression analysis showed that large VLDL and small LDL particles were negatively associated with bilirubin, whereas large HDL particles were associated positively with bilirubin (p < 0.05).ConclusionsIncreased triglycerides, as well as large VLDL and small LDL particles are associated negatively, whereas HDL cholesterol is associated positively with bilirubin in T2DM. The proposed pro-atherogenic effects of low bilirubin could in part be attributed to relationships with abnormalities in (apo)lipoproteins and lipoprotein subfraction characteristics.     

HDL 2 Particles are associated with hyperglycaemia,lower PON1 activity and oxidative stress in type 2 diabetes mellitus patients

ObjectivesIn this study we examined the relationship of oxidative stress and hyperglycaemia to antioxidative capacity of high-density cholesterol (HDL-C) particles in type 2 diabetes mellitus (DM).Design and methodsOxidative stress status parameters (superoxide anion (O₂^?), superoxide dismutase (SOD) activity and paraoxonase (PON1) status were assessed in 114 patients with type 2 DM and 91 healthy subjects. HDL particle diameters were determined by non-denaturing polyacrylamide gradient (3–31%) gel electrophoresis.ResultsPatients had significantly higher concentrations of oxidative stress parameter O₂^?(p < 0.001) and antioxidative defence, SOD activity (p < 0.001). Paraoxonase activity was significantly lower in diabetics (p < 0.001). The PON1₁₉₂ phenotype distribution among study groups was not significantly different. HDL 3 phenotype was significantly prevalent among patients (p < 0.001). Paraoxonase activity was significantly lower in patients with predominantly HDL 2 particles than in controls.ConclusionsThe results of our current study indicate that the diabetic HDL 2 phenotype is associated with hyperglycaemia, lower PON1 activity and elevated oxidative stress.     

Paraoxonase activity in athletes with depleted iron stores and iron-deficient erythropoiesis

ObjectiveThe aim of this study was to evaluate how conditions that precede anaemia (iron store depletion and iron-deficient erythropoiesis) affect human serum paraoxonase PON1 activity.Design and methodsBased on haemoglobin, transferrin saturation and serum ferritin values 119 athletes were divided into three groups: with iron depletion, with deficient erythropoiesis and controls. The following parameters were measured: paraoxonase activity towards paraoxon (POase) and diazoxon (DZOase), lipid hydroperoxides (LOOH), the pro-oxidant-antioxidant balance (PAB), red blood cells (RBC) and lipid status.ResultsSignificant differences were found between athletes with different stages of iron deficiency and controls with respect to PON 1 activity and oxidative stress status parameters (Wilks' Lambda = 0.712, F = 5.241, p < 0.001, η² = 0.156). There was no significant difference between the PON1 192 Q and R polymorphism distribution in the two groups of athletes with different stages of iron deficiency and controls (χ² = 1.086; p = 0.896). PON1 activity was positively correlated with RBCs, haemoglobin, transferrin saturation (p < 0.001) and ferritin (p = 0.037) and negatively correlated with LOOH (p = 0.044) in all three study groups.ConclusionsDeficient erythropoiesis in athletes contributes to impaired PON1 activity. In contrast, iron depletion, regardless of increased oxidative stress, does not affect PON1 activity.     

Measurement of oxidized lipoprotein (a) in patients with acute coronary syndromes and stable coronary artery disease by 2 ELISAs: Using different capture antibody against oxidized lipoprotein (a) or oxidized LDL

ObjectiveTo evaluate clinical value of oxidized lipoprotein(a) [ox-Lp(a)] levels.Design and methodsOx-Lp(a) were measured by 2 ELISAs using antibodies against ox-Lp(a) [ox-Lp(a)1] or oxidized low-density lipoprotein [ox-Lp(a)2], and studied in 161 acute coronary syndromes (ACS) patients, 114 stable coronary artery disease (CAD) and 100 control subjects.ResultsOx-Lp(a)1 was found related with ox-Lp(a)2 (r = 0.864, P = 0.000). Controlling for plasma lipids, Lp(a) and clinical characteristics, odds ratios of ox-Lp(a)1 on ACS and stable CAD were 5.06 (95% confidence interval 1.82–14.04) and 2.20 (0.78–6.22); those of ox-Lp(a)2 were 3.37 (1.07–10.63) and 1.35 (0.41–4.48), respectively. Receiver-operating characteristic curve analysis confirmed that performances of ox-Lp(a)1 were significantly superior to those for ox-Lp(a)2 in ACS (area: 0.803 vs. 0.723, P < 0.001) and stable CAD (area: 0.670 vs. 0.607, P < 0.01).ConclusionOx-Lp(a) levels using antibodies against ox-Lp(a) may represent a better risk marker than those using antibodies against oxidized low-density lipoprotein for ACS and stable CAD.     

Serum levels of vaspin and visfatin in patients with coronary artery disease—Kozani study

BackgroundThe association of novel adipokines, vaspin and visfatin, with atherosclerosis is still obscure. The present study aimed to investigate the relationship of those adipokines with the existence as well as the extent of coronary artery disease (CAD), suggesting a link between adiposity and atherosclerosis.MethodsWe enrolled a total of 108 patients with angiographically proven stable, asymptomatic CAD and 65 healthy controls (HC) without cardiovascular diseases. The severity of CAD was assessed using coronary angiography by the Gensini score. Clinical parameters, glycemic and lipid profile, high-sensitivity CRP (hsCRP), vaspin and visfatin levels were assayed.ResultsSerum levels of vaspin were significantly lower in subjects with CAD [0.91 (0.44–1.29) ng/ml] than healthy controls [1.42 (0.96–2.42) ng/ml] (p = 0.009). Inversely, visfatin (p = 0.016) and hsCRP (p < 0.001) levels were considerably up-regulated in CAD vs HC group. Multivariate analysis demonstrated decreased vaspin and increased visfatin levels to correlate with CAD presence, independent of other cardiovascular risk factors (p < 0.05). Standard multiple regression revealed HDL, LDL-C and vaspin to be independent determinants of Gensini score (R² = 0.189, p = 0.019). Notably, statin-free patients had even lower vaspin levels compared to statin users (p = 0.018).ConclusionsDecreased vaspin and increased visfatin serum levels were observed in asymptomatic patients with CAD. Low vaspin concentrations seemed to correlate with CAD severity.     

Evaluation of apolipoprotein M as a biomarker of coronary artery disease

ObjectiveTo investigate the possible role of apolipoprotein M (ApoM) in the development of coronary artery disease (CAD).Design and methodsCase-controlled study, which consisted of 118 CAD patients and 255 unrelated subjects used as control group. Plasma concentration of ApoM was determined by dot blot, severity of CAD was expressed with Gensini score or the numbers of lesioned coronary arteries, and serum lipid levels were also measured.Results and discussionOur study shows the mean level of plasma ApoM is 1.3757 ± 0.1493 ODu mm^? 2 in CAD patients, while it is 1.3502 ± 0.1288 ODu mm^? 2 in control group, and there are significant differences in plasma level of ApoM between two groups (t = 0.032, P < 0.05). Concentration of plasma ApoM is positively associated with plasma total cholesterol (r = 0.38, P = 0.025), high density lipoprotein cholesterol (r = 0.29, P = 0.03), low density lipoprotein cholesterol (r = 0.16, P = 0.03) and apolipoproein A–I (r = 0.24, P = 0.03). Multiple logistic and linear regression analysis showed that plasma concentration of ApoM did not correlate either with the number of lesioned coronaries or the Gensini score after adjusted for conventional cardiovascular risk factors (P > 0.05, respectively).ConclusionThe findings suggest that ApoM could not be an independent risk factor but a biomarker of CAD.     

Alteration of HDL functionality and PON1 activities in acute coronary syndrome patients

ObjectiveThe functionality of HDL has been suggested as an important factor in the prevention of cardiovascular and coronary artery diseases. The objective of the present study was to investigate the functionality of HDL and the factors that may affect the anti-atherogenic properties of HDL in ACS patients.Methods and resultsOne hundred healthy subjects and 205 ACS patients were recruited. HDL functionality was evaluated by measuring their capacity to mediate cholesterol efflux from J774 macrophages. Oxidative stress status was determined by measuring plasma malondialdehyde (MDA), protein carbonyl, and vitamin E levels by HPLC. The PON1 Q192R polymorphism status and PON1 paraoxonase and arylesterase activities of the healthy subjects and ACS patients were also determined. The HDL of ACS patients displayed a limited capacity to mediate cholesterol efflux, especially via the ABCA1-pathway. MDA (7.06 ± 0.29 μM) and protein carbonyl (9.29 ± 0.26 μM) levels were significantly higher in ACS patients than in healthy subjects (2.29 ± 0.21 μM and 3.07 ± 0.17 μM, respectively, p < 0.0001), while α- and γ-tocopherol (vitamin E) levels in ACS patients were 8-fold (p < 0.001) and 2-fold (p < 0.05) lower than in healthy subjects. Paraoxonase, arylesterase and HDL-corrected PON1 activities (PON1 activity/HDL ratio) were significantly lower in ACS patients. Logistic regression analyses showed that high PON1 paraoxonase and arylesterase activities had a significant protective effect (OR = 0.413, CI 0.289–0.590, p < 0.001; OR = 0.232 CI 0.107–0.499, p < 0.001, respectively) even when adjusted for HDL level, age, BMI, and PON1 polymorphism.ConclusionThe results of the present study showed that the functionality of HDL is impaired in ACS patients and that the impairment may be due to oxidative stress and an alteration of PON1 activities.     

Plasma proprotein convertase subtilisin–kexin type 9 is predominantly related to intermediate density lipoproteins

ObjectivesProprotein convertase subtilisin–kexin type 9 (PCSK9) is a key regulator of low density lipoprotein (LDL) receptor processing, but the PCSK9 pathway may also be implicated in the metabolism of triglyceride-rich lipoproteins. Here we determined the relationship of plasma PCSK9 with very low density lipoprotein (VLDL) and LDL subfractions.Design and methodsThe relationship of plasma PCSK9 (sandwich enzyme-linked immunosorbent assay) with 3 very low density lipoprotein (VLDL) and 3 low density lipoprotein (LDL) subfractions (nuclear magnetic resonance spectroscopy) was determined in 52 subjects (30 women).ResultsIn age- and sex-adjusted analysis plasma PCSK9 was correlated positively with total cholesterol, non-high density lipoprotein cholesterol and LDL cholesterol (r = 0.516 to 0.547, all p < 0.001), as well as with triglycerides (r = 0.286, p = 0.044). PCSK9 was correlated with the VLDL particle concentration (r = 0.336, p = 0.017) and with the LDL particle concentration (r = 0.362, p = 0.010), but only the relationship with the LDL particle concentration remained significant in multivariable linear regression analysis. In an analysis which included the 3 LDL subfractions, PCSK9 was independently related to intermediate density lipoproteins (IDL) (p < 0.001), but not to other LDL subfractions.ConclusionsThis study suggests that plasma PCSK9 predominantly relates to IDL, a triglyceride-rich LDL subfraction. The PCSK9 pathway may affect plasma triglycerides via effects on the metabolism of triglyceride-rich LDL particles.     

Circulating sTWEAK improves the prediction of coronary artery disease

ObjectivesDecreased concentrations of circulating soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) were recently reported to be associated with atherosclerosis, but there are still no data concerning its predictive performance.Design and methodsThe current cross-sectional study investigates the potential of the novel atherosclerotic biomarker for the prediction of coronary artery disease (CAD). Serum sTWEAK was measured by ELISA in 76 CAD patients and 82 CAD-free subjects.ResultsSerum sTWEAK concentrations were significantly lower in the patients (534.5 ± 110.9 μg/L) than in the controls (688.1 ± 150.0 μg/L, p < 0.001), even after adjusting for different confounders (p < 0.001). The areas under ROC curves (AUC)s calculated for logistic regression models that included different known risk factors were significantly increased when sTWEAK was added to the corresponding model (p = 0.011–0.035).ConclusionsThe measurement of serum sTWEAK concentrations improves the prediction of CAD based on existing biomarkers.     

Time of sampling is crucial for measurement of cell-free plasma DNA following acute aseptic inflammation induced by exercise

ObjectivesTo determine the time-course changes of cell-free plasma DNA (cfDNA) following heavy exercise.MethodscfDNA concentration, C-reactive protein levels (hs-CRP), uric acid concentration (UA), creatine kinase activity (CK) were measured before and post-exercise (immediately post, 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 24 h).ResultscfDNA increased (15-fold) 30-min post-exercise and normalized thereafter. hs-CRP increased (56%, p < 0.001) 1 h post-exercise, remained elevated throughout recovery (52–142%, p < 0.0001), and peaked (200% rise, p < 0.0001) at 24 h post-exercise. UA and CK increased (p < 0.05), immediately post-exercise, remained elevated throughout recovery (p < 0.0001), and peaked (p < 0.0001) at 24 h of post-exercise recovery.ConclusionscfDNA sampling timing is crucial and a potential source of error following aseptic inflammation.     

Effect of valproic acid treatment on copper availability in adult epileptic patients

ObjectivesIn rats a significant increase of the copper biliary excretion is produced by valproic acid administration, however, a conclusive study on the possible appearance of copper deficiency in humans during treatment with this drug has still not been carried out.Design and methodsIn 101 adult epileptic patients treated in monotherapy (n = 75) and polytherapy (n = 26) with valproic acid, and 50 healthy controls, were determined serum copper, immunoreactive ceruloplasmin and its oxidase activity against o-dianisidine, in order to calculate the specific oxidase activity (activity per unit mass of enzyme protein) and copper/ceruloplasmin ratio.ResultsSpecific oxidase activity of ceruloplasmin and copper/ceruloplasmin ratio were significantly lower in the groups of patients treated with valproic acid than in the controls. Significant correlations were obtained between both biochemical variables (p < 0001). In 38% of the patients treated in mono or polytherapy, the specific oxidase activities of ceruloplasmin were smaller than the estimated lower limit of reference.ConclusionsThese results, possible due to a diminished copper content of the circulating ceruloplasmin, suggest that marginal or moderate copper deficiency may have a substantial prevalence among patients treated with valproic acid.     

The detection of autoantibodies to ATP-binding cassette transporter A1 and its role in the pathogenesis of atherosclerosis in patients with systemic lupus erythematosus

ObjectivesTo investigate the prevalence of autoantibodies against ATP-binding cassette transporter A1 (ABCA1) in SLE patients, and evaluate the association between anti-ABCA1 autoantibodies and atherosclerosis in SLE.Design and methodsThe sera of 75 SLE patients and 75 healthy controls were tested by immunoblotting. Then, we examined the effect of anti-ABCA1 autoantibodies on cholesterol efflux in vitro.ResultsThe prevalence of anti-ABCA1 antibodies in SLE patients was significantly higher than the controls (p < 0.05). The prevalence in the SLE-plaque group was higher than that in the SLE-non-plaque group (p < 0.05). The IgG purified from anti-ABCA1-antibody positive sera can inhibit cellular cholesterol efflux from THP-1 cells in vitro with a significantly higher inhibition ratio than that of the healthy controls.ConclusionsOur observations suggest that anti-ABCA1 autoantibodies are involved in the pathogenesis of lupus atherosclerosis and that autoantibodies against ABCA1 may act as biomarkers for atherosclerosis in SLE.     

Antioxidant status and lipid peroxidation in the blood of breast cancer patients of different ages after chemotherapy with 5-fluorouracil,doxorubicin and cyclophosphamide

ObjectivesBreast carcinoma is related to the increase of lipid peroxidation in plasma with concomitant decrease of antioxidant (AO) defense capacity in blood cells, which becomes more pronounced during aging of the patients. This work evaluated the potential age-related effect of chemotherapy with 5-fluorouracil, doxorubicin and cyclophosphamide (FAC) on the level of lipid hydroperoxides (LP), glutathione (GSH), AO enzyme activities of copper, zinc superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) in breast cancer patients. The level of CuZnSOD protein was assessed after the FAC therapy and radiotherapy of breast cancer.Design and methodsAO parameters were measured in the blood of 58 breast cancer patients and 60 healthy age-matched healthy subjects by biochemical and Western blot analyses.ResultsIncreased oxidative stress (LP: p < 0.05) and decreased AO enzyme activities (CuZnSOD: p < 0.01, GPx: p < 0.05, GR: p < 0.01) and GSH level (p < 0.01) in the blood of breast cancer patients in response to FAC chemotherapy seem not to be age-dependent. CuZnSOD enzyme expression decreased after the FAC chemotherapy (p < 0.05), while it increased after the radiotherapy of breast cancer (p < 0.05).ConclusionFAC chemotherapy and radiotherapy promote further oxidative shift, which potentiate already existing chronic oxidative stress linked to breast cancer. In these effects, impaired capacity for H₂O₂ detoxification (CAT, GPX and GSH) seems to have major contribution.     

Influence of pre-analytical and analytical factors on osteoprotegerin measurements

IntroductionOsteoprotegerin (OPG), an osteoclastogenesis inhibitor implicated in bone remodelling, has emerged as a potential biomarker for cardiovascular disease. In order to implement OPG determination in the clinical laboratory, it is crucial to identify the most appropriate specimen type, preparation and measurement conditions. The present study focuses on identifying the pre-analytical variables that may influence OPG measurements.MethodsSerum and plasma (in EDTA, heparin and citrate) were collected from 45 healthy volunteers (men (n = 21, 46.7%), women (n = 24, 53.3%)). OPG was analysed by ELISA. The influence of the centrifugation speed, the number of freeze–thaw cycles, delay in sample processing, thermo-stability and endogenous interfering agents (haemolysis, triglycerides, bilirubin, cholesterol and RANKL) were studied.ResultsOPG concentrations were significantly lower (p < 0.0001) in serum (1015 ± 357 pg/mL) than in all plasma samples (1314 ± 448 pg/mL in EDTA, 1209 ± 417 pg/mL in heparin and 1260 ± 498 pg/mL in citrate).Increasing centrifugation speed (200 g to 3000 g) did not change serum OPG concentration (p = 0.88). However, OPG concentration significantly increased when centrifuged serum samples were stored at 48 h at room temperature (p < 0.0001). Repeated freeze–thaw cycles did not modify OPG levels until 4 cycles (p < 0.0001). Increasing time before processing the samples (2 h and 6 h) raised OPG concentrations both at room temperature (p < 0.0001) or 4 °C (p < 0.001).Positive concentration-dependent interference of triglycerides was found in the analysed pooled samples; however, OPG concentrations were falsely diminished with haemoglobin interference. Bilirubin, cholesterol and RANKL did not interfere with OPG measurements.     

Proatherogenic disturbances in lipoprotein profile,associated enzymes and transfer proteins in women with iron deficiency anaemia

ObjectiveTo characterize the lipid-related atherogenic risk factors in iron deficiency anaemia (IDA) patients.Design and methodsTwenty IDA women were compared to healthy age-matched controls. Lipoprotein profile, cholesteryl ester transfer protein (CETP), paraoxonase (PON) 1 and lipoprotein-associated phospholipase A₂ (LpPLA₂) activities and plasma levels of oxidized-LDL were evaluated.ResultsTriglycerides were higher (median [range]) (1.0 [0.5–1.9] vs. 0.7 [0.5–1.5] mmol/L, p < 0.05) and HDL-C lower (mean ± SD) (1.3 ± 0.3 vs. 1.6 ± 0.4 mmol/L, p < 0.01) in the patients group. CETP (197 ± 29% vs. 151 ± 29% mL^? 1 h^? 1, p < 0.001), PON 1 (122 ± 17 vs. 140 ± 33 μmol mL^? 1 min^? 1, p < 0.05) and LpPLA₂ (9.6 ± 2.0 vs. 8.1 ± 1.7 μmol mL^? 1 h^? 1, p < 0.05) activities were different in IDA women. No difference was observed in oxidized-LDL. Haemoglobin correlated negatively with triglycerides (r = ? 0.35, p < 0.05), CETP (r =  ?  0.62, p < 0.001) and LpPLA₂ (r =  ?  0.34, p < 0.05), while ferritin was positively associated with HDL-C (r =  0.39, p < 0.05) and inversely with CETP (r =  ?  0.49, p < 0.005).ConclusionThe alterations in lipoprotein profile, CETP, PON 1 and LpPLA₂ activities described in the present study indicate that non-treated IDA might represent a proatherogenic state.     

Growth-differentiation factor-15 and tissue doppler ımaging in detection of asymptomatic anthracycline cardiomyopathy in childhood cancer survivors

ObjectivesAnthracyclines have led to an increased risk of cardiac morbidity and mortality. Late cardiac complications in cancer survivors may develop from subclinical myocardial damage. Tissue Doppler imaging (TDI) also has potential as a clinically useful technique for the assessment of myocardial function. Biochemical markers may be used to detect cardiac damage growth-differentiation factor-15 (GDF-15) and are emerging as a biomarker of cardiac dysfunction. The aim of this study is to assess the value of the plasma levels of GDF-15 and TDI in detecting late myocardial dysfunction in childhood cancer survivors (CCS) who were treated with anthracyclines.Design and methodsThirty-eight CCS who had completed chemotherapy treatment with anthracyclines were included in this study. Control group consisted of 32 age- and gender-matched healthy volunteers. All children underwent a detailed echocardiography, which contained an M-mode, pulse Doppler and tissue Doppler imaging. However, GDF-15 and cardiac troponin-I (cTnI) were measured.ResultsAlthough, systolic function of the left ventricular was similar in all groups, there were significant differences between parameters of diastolic function of the heart. The mitral valve E wave, E/A ratio, left ventricular E′m wave, and E′m/A′m ratio were different in the patients than in the controls (p = 0.049, p = 0.037, p < 0.0001, p = 0.001, respectively). The tricuspid valve E/A ratio, right ventricular E′t wave, and E′t/A′t ratio in the patients were also different from those of the controls (p = 0.031, p < 0.0001, p < 0.0001, respectively). Mean plasma GDF-15 was significantly higher in patients than healthy controls (p = 0.027). There were no significant differences in cTnI between both groups.ConclusionsGrowth-differentiation factor-15 level may be used as a biomarker of anthracycline-induced cardiovascular disease severity in the CCS.     

Effects of lifestyle modification on oxidized LDL,reactive oxygen species production and endothelial cell viability in patients with coronary artery disease

ObjectivesWe evaluated the effects of lifestyle modification (LM) on lipid profile, oxidative stress and serum-stimulated human coronary artery endothelial cell (HCAEC) viability in coronary artery disease (CAD) patients after 6 months.Design and methodsThirty patients with CAD were randomly assigned to LM intervention (n = 15) and usual care control (n = 15) groups. LM-intervened patients were instructed to consume low-fat, high-antioxidants and fiber diets. Moderate exercise and stress management were also advised. Group support to maintain patients' compliance was applied.ResultsSerum cholesterol, triglyceride, oxidized LDL and protein carbonyl were decreased in LM group. Serum triglyceride was increased in control group. HCAEC viability was increased, while intracellular reactive oxygen species was decreased, by serum from the LM group.ConclusionLM is capable of improving lipid profile, reducing oxidative stress and increasing HCAEC survival in the patients with CAD, hence lowering a risk for the future cardiovascular event.     

Sperm head defects and disturbances in spermatozoal chromatin and DNA integrities in idiopathic infertile subjects: Association with cigarette smoking

ObjectivesTo evaluate sperm chromatin and DNA integrities in idiopathic infertile men and determine the possible association(s) of cigarette smoking on oxidative stress markers, antioxidant capacity and semen quality.Subjects and methodsSemen samples from men referring to the andrology laboratory were categorized into 3 groups: fertile non-smokers (n = 16), infertile non-smokers (n = 36), and infertile smokers (n = 34). Semen analysis was performed according to WHO criteria. The percentage of sperm DNA fragmentation index (%DFI) and the percentage of sperm with abnormally high DNA stainability (HDS%; immature spermatozoa) were determined by SCSA using the metachromatic properties of acridine orange. Lipid peroxidation, superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) levels in seminal plasma and spermatozoa were measured by spectrophotometric assays.ResultsThe classical semen parameters were negatively correlated with lipid peroxidation in spermatozoa; motility and morphology were negatively correlated with %DFI (p < 0.05). HDS% was also negatively correlated with above markers except for morphology (r = ? 0.352, p = 0.081). DFI% and HDS% were significantly higher in the infertile smokers group than in infertile non-smokers (p = 0.032; p = 0.001 respectively). Cigarette smoking was significantly associated with DFI%, HDS%, TBARS and the fraction of “round-headed” sperm (r = 0.796, p = 0.0001; r = 0.371, p = 0.033; r = 0.606, r = 0.591, p = 0.001 respectively), and decreased SOD levels (r = ? 0.545).ConclusionDFI%, HDS% and round-head sperms are increased in idiopathic infertile men; this increase is associated with cigarette smoking. These defects may be attributed to increased oxidative stress and insufficient scavenging antioxidant enzymes in the seminal fluid of infertile patients.     

Mutations in APOA-I and ABCA1 in Norwegians with low levels of HDL cholesterol

BackgroundEpidemiological studies have shown that low levels of plasma high density lipoprotein (HDL) cholesterol are associated with increased risk of ischemic heart disease (IHD), but it appears that genetic forms of low HDL cholesterol levels, as opposed to lifestyle-induced low levels of HDL cholesterol, do not result in increased risk of IHD. Therefore, the etiology of reduced levels of plasma HDL cholesterol may represent a factor that should be considered in risk stratification with respect to primary prevention. Genes encoding proteins involved in HDL metabolism, such as the ATP-binding cassette transporter A1 (ABCA1) and apolipoprotein (apo) A-I genes, are candidate genes for harboring mutations that lead to low HDL cholesterol levels.MethodsThe ABCA1 and apoA-I genes in 56 Norwegian patients, with a mean HDL cholesterol level of 0.53 (± 0.15) mmol/l, were subjected to DNA sequencing.ResultsSeveral mutations were identified in the ABCA1 gene, and two mutations were identified in the apoA-I gene. A total of 18 patients (32%) were carriers of mutations considered to be pathogenic. Their mean HDL cholesterol level was 0.45 (± 0.15) mmol/l compared to 0.57 (± 0.14) mmol/l in noncarriers (p < 0.005).ConclusionMutations in the genes encoding ABCA1 and apoA-I are common in Norwegians, with a markedly decreased HDL cholesterol level.