Plasma ox-LDL Levels Research Articles

DUSP1 Is a Potential Marker of Chronic Inflammation in Arabs with Cardiovascular Diseases.

Background Cardiovascular disease (CVD) risks persist in patients despite the use of conventional treatments. This might be due to chronic inflammation as reflected in epidemiological studies associating circulating low-grade inflammatory markers with CVD recurrent events. Here, we explored this potential link by assessing plasma dual-specificity phosphatase 1 (DUSP1) levels and comparing them to high-sensitivity CRP (hsCRP) and oxidized low-density lipoprotein (oxLDL) levels and their associations to conventional CVD risk factors in confirmed CVD patients. Methods Human adults with reported CVD (n = 207) and controls (n = 70) living in Kuwait were used in this study. Anthropometric and classical biochemical parameters were determined. Plasma levels of DUSP1, oxLDL, and hsCRP were measured using human enzyme-linked immunosorbent assay kits. Results DUSP1 and hsCRP plasma levels and their least square means were higher in CVD cases, while oxLDL plasma levels were lower (p < 0.05). Multivariate logistic regression analysis showed that DUSP1 and hsCRP are independently associated with CVD in the studied population, as reflected by 2-fold and 1.5-fold increased risks with increased levels of DUSP1 and hsCRP, respectively. In our study, DUSP1 levels were found to be associated with CVD despite statin treatment and diabetes status (p < 0.05), whereas hsCRP mainly correlated with obesity markers. Conclusions Circulating DUSP1 might be a predictor of chronic subclinical inflammation and residual risk in CVD patients, whereas our data suggest that the association between hsCRP and CVD is largely accounted for adiposity risk factors.

Relationship of fruit and vegetable intake to dietary antioxidant capacity and markers of oxidative stress: A sex-related study.

Oxidative stress contributes to the development of chronic diseases. Fruits and vegetables contain several phytonutrients (carotenoids, polyphenols) that exert antioxidant effects. The aim of this study was to investigate sex differences in fruit and vegetable intake, and the relationship to plasma levels of carotenoids as well as to total antioxidant capacity (pTAC). We studied also sex differences in the relationship between fruit and vegetables intake and plasma levels of lipid hydroperoxides, as well as of oxidized low-density lipoprotein (ox-LDL). This study included 83 healthy adults (35 men and 48 women, mean age 40 ± 10 y). Dietary intake of carotenoids and total antioxidant capacity (dTAC) were evaluated on the basis of a 15-d food frequency questionnaire. Plasma levels of β-carotene, lutein, and pTAC were studied. Moreover, levels of plasma lipid hydroperoxides and ox-LDL were evaluated using the ferrous oxidation-xylenol orange 2 (FOX2) assay and a monoclonal antibody-based enzyme-linked immunosorbent assay procedure, respectively. Dietary habits were sex-related with a higher intake of fruits and vegetables (P < 0.05) and β-carotene (P < 0.001) in women than in men. Mean values of plasma lutein and β-carotene were higher in women than in men. Mean values of ox-LDL and lipid hydroperoxides were higher in men than in women (P < 0.05). Significant negative correlations were established between the individual values of ox-LDL and the levels of lutein versus β-carotene and versus pTAC values in plasma in both groups. Individuals belonging to the tertile with the highest daily intake of fruits and vegetables or the highest daily dTAC showed the lowest levels of plasma ox-LDL. In each category, sex-related differences were observed with men showing higher levels of ox-LDL than women. Moreover, lower levels of plasma β-carotene were observed in men in each tertile of daily intake of fruits and vegetables compared with females. Based on the data obtained, we confirm that high fruit and vegetable consumption exerts a positive effect on antioxidant defenses and decreases oxidative damage of plasma lipoproteins for both sexes. The results suggest that the protective effect can be found to a higher extent in women than in men. Sex-based differences are apparent in many chronic diseases. Thus, a higher consumption of antioxidant-rich fruits and vegetables should be recommended in efforts to prevent diseases in which sex-related differences in oxidative stress play a considerable role.

OxLDL plasma levels in patients with Alzheimer's disease.

The objective of this study was to characterize the conventional lipid profile, oxLDL levels and ApoE polymorphism in patients with Alzheimer's disease (AD) and in elderly individuals without cognitive impairment. Eighty elderly individuals were selected and the levels of oxLDL were determined using the ELISA kit, and ApoE gene polymorphism was investigated using polymerase chain reaction-restriction fragment length polymorphism. Significantly reduced levels of oxLDL were observed in patients with AD compared to the control group. A higher frequency of the ApoE ε4 allele was observed in patients with AD compared to controls. No difference was observed for total cholesterol, HDL-C, and LDL-C levels between the two groups, while triglyceride levels were higher in controls compared with patients with AD. The data analyzed together did not reveal significant differences in lipid profiles, including oxLDL levels. However, the importance of lipid changes in the genesis of the disease cannot be ruled out. Nevertheless, the ApoE ε4 allele was significantly more frequent in patients with Alzheimer's dementia in agreement with previous findings in the literature, but this genetic component did not change the levels of oxLDL.

The relationship between oxidized low-density lipoprotein and the NIHSS score among patients with acute ischemic stroke: The SOS-Stroke Study

Background and aimsOxidized low-density lipoprotein (oxLDL) has a defined role in the genesis and development of atherosclerosis, however, whether it is related to severity of neurological deficits is rarely reported. The aim of our study was to investigate the potential association between oxLDL and the National Institutes of Health Stroke Scale (NIHSS) score among patients with acute ischemic stroke. MethodsBetween January 2014 and October 2014, we recruited 4111 patients with acute ischemic stroke (AIS), who were admitted within 7 days–43 hospitals in China, and participated in the SOS-Stroke Study. We collected detailed clinical data and then tested the relationship between oxLDL and the NIHSS score using a multivariate linear regression analysis. ResultsAfter adjusting for age, gender, ethnicity, marriage and other confounding variables, the elevated NIHSS score was significantly associated with increased oxLDL levels, and each 1-μg/dL elevation in oxLDL concentration resulted in an increase of 0.027 in the NIHSS score. ConclusionsA positive correlation was found between plasma levels of oxLDL and the NIHSS score in patients with acute ischemic stroke. Higher plasma levels of oxLDL potentially suggest a worse prognosis in AIS patients.

Consumption of seafood and its estimated heavy metals are associated with lipid profile and oxidative lipid damage on healthy adults from a Spanish Mediterranean area: A cross-sectional study

The association between the consumption of seafood and its benefits on cardiovascular (CVD) risk can be challenged by its heavy metal (HM) content. This study aimed to explore the association of seafood consumption and its estimated HM contents with the lipid profile and lipid oxidation biomarkers in adults from a Spanish Mediterranean area who do not present risk factors for CVD.In this cross-sectional study, the clinical history, three-day dietary record, lipid profile (LDLc, HDLc, APOB/A, and triglyceride levels), plasma oxidised LDL (oxLDL) and 8-isoprostane levels of 81 adults without risk factors for CVD [43% men, with a mean age of 43.6 years (95%CI: 40.1–47.1)] were assessed. The HM [arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb)] contents of seafood were estimated according to data from analyses of marine species in the same Mediterranean area. Moderate adherence to the Mediterranean diet (score: 4.6 of 9) with a mean seafood consumption of 74.9g/day (95%CI: 59.9–89.9), including 22.7g of shellfish per day (95%CI: 13.5–31.9), was observed. The estimated HM contents were lower than the provisional tolerable weekly intakes (PTWIs): 21.12µg/kg/week As, 0.57µg/kg/week InAs, 0.15µg/kg/week Cd, 1.11µg/kg/week Hg and 0.28µg/kg/week Pb.After adjusting by confounder variables, an increase in shellfish consumption was associated with increases in the levels of LDLc (P=0.013), non-HDLc (P=0.015), APOB/A (P=0.02) and plasma oxLDL (P=0.002). Moreover, an increase in the estimated As and Hg levels in shellfish was associated with an increase in LDLc (P=0.015 and P=0.018, respectively), non-HDLc (P<0.008 and P<0.008, respectively), APOB/A ratio (P=0.008 and P=0.009, respectively), and oxLDL (P≤0.001 and P≤0.001, respectively) levels.In conclusion, in adults without risk factors for CVD, increasing shellfish consumption, even by a moderate amount, could favour a pro-atherogenic lipid profile and a higher level of oxidised LDL. These associations are likely influenced by the estimated exposure to As and Hg from shellfish despite these values are lower than the PTWIs.

Platelet bound oxLDL shows an inverse correlation with plasma anaphylatoxin C5a in patients with coronary artery disease

Both oxidized lipids as well as the complement system contribute to atherothrombosis. The expression of complement receptors correlates with the expression of platelet activation markers, and platelet bound oxidized low-density lipoprotein (oxLDL) modulates platelet function. In the present study, we investigated the relationship of markers of complement activation, the anaphylatoxins C5a and C3a, and oxidized low-density lipoprotein.Two hundred and seven patients with coronary artery disease (CAD) were analyzed in this study. Using enzyme-linked immunosorbent assays, plasma levels of oxLDL, C3a, and C5a were measured. Moreover, we assessed platelet bound oxLDL by flow cytometry. The overall level of C5a in the troponin negative group (stable angina (SA) and unstable angina (UA)) compared to the troponin positive group (non-ST-elevation myocardial infarction (NSTEMI) and ST-elevation myocardial infarction (STEMI)) did not differ significantly (62.7 ± 32.4 ng/ml versus 65.8 ± 40.3 ng/ml). While C5a and C3a showed a significant correlation with each other (r = 0.25, p < 0.001), there was no statistically significant relationship between C3a and platelet bound oxLDL (r = 0.06, p = 0.37). Furthermore, plasma oxLDL did not correlate with either C3a or C5a. However, we observed a moderate, yet significant negative correlation between plasma C5a and platelet bound oxLDL (r = −0.15, p = 0.04). Partial correlation analysis correcting for the presence of acute coronary syndrome (ACS), troponin status or the subgroups SA, UA, NSTEMI, or STEMI did not alter this correlation substantially. Interestingly, flow cytometric analysis of human platelets showed increased expression of C5aR and P-selectin after in vitro stimulation with oxLDL.In conclusion, the complement anaphylatoxin C5a shows an inverse correlation with platelet bound oxLDL. The relationship of oxidized lipids to particular complement components may add to the platelet–lipid interplay in atherogenesis and trigger future clinical and mechanistic studies.

Oxidized-LDL, Toll-like Receptor 4, Lipocalin 2 and Omentin1: Role in Diabetic Nephropathy

Background: Diabetic nephropathy is the major micro-vascular complication of type 2 diabetes mellitus (T2DM) and is the main cause for end-stage kidney disease. In view of metabolic derangements of T2DM, we went further to investigate the role played by oxidized low density lipoprotein (ox-LDL), toll like receptor 4 (TLR4), lipocalin-2 (LCN2), and omentin-1 in DN. Patients and Methods: 15 normo-albuminuria T2DM, 15 micro-albuminuria T2DM and 15 macroalbuminuria T2DM in addition to 15 apparently healthy volunteer who served as control group were enrolled in this study. Demographic and clinical data were recorded. Plasma Ox-LDL, omentin1 and urinary LCN2 levels by immunoassy and TLR4 mRNA level with real time PCR were assessed. Results: TLR4 gene expression, Plasma ox-LDL, urinary LCN2 levels were increased in T2DM cases as compared to their allied control group with the higher values were for macro-albuminuria Original Research Article Keshk and Esheba; IJBCRR, 11(4): 1-9, 2016; Article no.IJBCRR.25286 2 T2DM cases. Meanwhile Plasma omentin-1 level was decreased in T2DM cases when compared to their allied control group with least values were for macro-albuminuria T2DM cases. Also there were positive correlations between TLR4 mRNA, ox-LDL, urinary LCN2 levels and serum creatinine, fasting blood glucose, urinary albumin/creatinine ratio. Meanwhile, omentin 1 showed negative correlations with serum creatinine, fasting blood glucose, urinary albumin/creatinine ratio. Conclusions: Ox-LDL, TLR4, LCN2 and omentin 1 may confer a relevant role in diabetic nephropathy development and progression.

The Relationship of Plasma miR-29a and Oxidized Low Density Lipoprotein with Atherosclerosis

Background/Aims: Atherosclerosis is a chronic inflammatory condition associated with a variety of vascular diseases. Previous studies showed that both miR-29a and oxidized low density lipoprotein (ox-LDL) were vital in the development of atherosclerosis. However, the relationship between miR-29a and ox-LDL remains unknown. This study was designed to investigate the association of miR-29a and ox-LDL and to test whether circulating miR-29a and ox-LDL levels could predict atherosclerosis. Methods: In 170 participants, plasma levels of miR-29a were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) while plasma ox-LDL levels were determined using enzyme-linked immunosorbent assay (ELISA) kits. The relationship between miR-29a level and ox-LDL and carotid intima-media thickness (cIMT) was assessed using the Spearman correlation coefficient and multiple liner regression. Results: Compared with the normal cIMT group, the increased cIMT group had higher levels of ox-LDL (0.47 ± 0.08 vs 0.29 ± 0.06 ng/ml, p = 0.003) and miR-29a (32.93 ± 4.26 vs 26.37 ± 1.04, p < 0.001). A positive correlation was found between ox-LDL and miR-29a (r = 0.695, p < 0.001), and both the ox-LDL (r = 0.857, p < 0.001) and the miR-29a (r = 0.753, p < 0.001) were positively related to cIMT. Furthermore, multiple liner regression indicated that a significant correlation between ox-LDL and cIMT (β = 0.768, p < 0.001), as well as between miR-29a and cIMT (β = 0.686, p <0.001). The combination of miR-29a and ox-LDL (AUC = 0.926, p < 0.001) offered a better predictive value for atherosclerosis than either miR-29a (AUC = 0.759, p < 0.001) or ox-LDL (AUC = 0.762, p < 0.001) alone. Conclusion: Increased miR-29a and ox-LDL levels were associated with an early stage of atherosclerosis, and the combination of miR-29a and ox-LDL offered better predictive values for atherosclerosis than either alone.

LOX-1 gene variants and maternal levels of plasma oxidized LDL and malondialdehyde in patients with gestational diabetes mellitus.

The aim of this study was to investigate the relationships between the maternal levels of oxidized LDL (ox-LDL), lipid peroxidation marker malondialdehyde (MDA) and LOX-1 3'UTR188C/T and K167N single nucleotide polymorphisms in pregnant Turkish women with gestational diabetes mellitus (GDM). 116 pregnant women with GDM and 120 healthy pregnant women from the same geographic region were included in the study. Polymerase chain reaction-based restriction analysis was used to identify 3'UTR188C/T and K167N polymorphisms of the LOX-1 gene. Plasma ox-LDL and MDA levels were determined by enzyme-linked immunosorbent assay and spectrophotometric method in all study subjects, respectively. Our results indicated that the distribution of the LOX-1 3'UTR188C/T and K167N genotypes and alleles did not differ significantly among subjects with or without GDM (p > 0.05). TT and NN genotype carriers are associated with some glucose metabolism parameters (p < 0.05). There were no significant differences among plasma ox-LDL and MDA levels with regard to LOX-1 3'UTR188C/T and K167N polymorphisms in GDM group and control subjects (p > 0.05). According to the combined genotype analysis of LOX-1 3'UTR 188 TT and K167N NN polymorphisms, plasma MDA and ox-LDL levels were significantly different between women with GDM and healthy subjects either with or without combined TT/NN genotype carriers (p < 0.001). According to our results, ox-LDL and MDA levels were increased in GDM pregnant women and healthy pregnant women either with or without combined TT/NN genotype carriers, for our Turkish sample, these genotype carriers appear to be related with increased oxidative stress in patients with GDM.

Oxidized LDL Levels Are Increased in HIV Infection and May Drive Monocyte Activation.

HIV infection is associated with increased cardiovascular risk, and this risk correlates with markers of monocyte activation. We have shown that HIV is associated with a prothrombotic monocyte phenotype, which can be partially mitigated by statin therapy. We therefore explored the relationship between oxidized low-density lipoprotein (oxLDL) particles and monocyte activation. We performed phenotypic analysis of monocytes using flow cytometry on fresh whole blood in 54 patients with HIV and 24 controls without HIV. Plasma levels of oxLDL, soluble CD14, IL-6, and soluble CD163 were measured by enzyme-linked immunosorbent assay. In vitro experiments were performed using flow cytometry. Plasma levels of oxLDL were significantly increased in HIV infection compared with controls (60.1 units vs. 32.1 units, P < 0.001). Monocyte expression of the oxLDL receptors, CD36 and Toll-like receptor 4, was also increased in HIV. OxLDL levels correlated with markers of monocyte activation, including soluble CD14, tissue factor expression on inflammatory monocytes, and CD36. In vitro stimulation with oxLDL, but not to low-density lipoprotein, resulted in expansion of inflammatory monocytes and increased monocyte expression of tissue factor, recapitulating the monocyte profile we find in HIV disease. OxLDL may contribute to monocyte activation, and further study in the context of HIV disease is warranted.

High plasma levels of oxidatively modified low-density lipoproteins are associated with the suppressed expression of immunomodulatory molecules in patients with hematological malignancies.

Dyslipidemia is a common feature in immunosuppressed patients, such as kidney and bone marrow transplantation recipients and patients with breast, prostate or gynecological carcinoma or acute lymphoblastic leukemia. In addition, high levels of oxidatively modified low-density lipoproteins (oxLDLs) are closely associated with carcinogenesis. There are, however, no reports on the association between the serum oxLDL levels and the expression of important immunomodulatory molecules in patients with hematological disorders. In the present study, 39 patients with hematological disorders were stratified into four groups: Two groups with malignancies [chronic myeloid leukemia (CML) and acute myeloblastic leukemia (AML)] and two groups without malignancies [myelodysplastic syndrome (MDS) and iron deficiency anemia (IDA)]. Immunomodulatory molecules were monitored in these groups. The enzyme-linked immunosorbent assay results indicated that the plasma oxLDL levels were significantly higher in patients with AML or CML than those in patients with MDS or IDA. The quantitative polymerase chain reaction results revealed that the expression of numerous important immunomodulatory elements, including tumor-related genes, immunological and inflammatory cytokines, defense-responsive genes, genes regulating cell proliferation, adhesion and migration molecules and leukocyte chemotaxis genes, showed considerable variation in patients with hematological disorders, particularly in those with MDS or IDA, as compared with the expression in the healthy volunteers. The present study demonstrated that, in patients with a hematological malignancy (either AML or CML), the activation of numerous immune response-related molecules was inhibited. Thus, an association between hematological malignancies and dyslipidemia, i.e. high levels of oxLDL, is suggested. Further research is necessary to investigate how oxLDL influences cancer progression.

0143: Serum thiolactonase activity and paraoxonase gene polymorphism in coronary artery Tunisian patients with or without diabetes

Serum homocysteine thiolactonase activity is closely related to homocysteine and ox-LDL levels in coronary artery disease patients. Homocysteine thiolactonase activities are the result of environmental factors and genetic polymorphisms of paroxosonase. The relevance of gene polymorphism in coronary patients with or without diabetes was investigated in a case-control study. The population included 140 control subjects, 47 coronary artery disease patient without diabetes and 44 patients with type 2 diabetes. Serum thiolactonase activity decreased significantly in coronary artery disease patients: 318.9±156 U/l those without diabetes and 388.8±180 in the diabetic ones compared with the controls: 568.8±250U/l (p<0.001). These activities were associated with increased plasma homocysteine and ox-LDL levels (p<0.001). The paroxonase allele frequency is significantly higher in controls than coronary artery patients (p<0.001). The frequency of R high activity allele was also higher in diabetic coronary patients (11.3%), than in those without diabetes (4.2%). No significant association was found between paroxonase LN gene polymorphisms and diabetes in coronary patients. The difference in allele frequency for the paroxonase R gene polymorphism may be the cause of the high thiolactonase activity observed in coronary patients with type 2 diabetes mellitus. Further studies are needed to be conducted to elucidate the role of the enzyme in the development of vascular complications in these patients.

The association of lectin-like oxidized LDL receptor 1 (LOX-1) K167N and 3'UTR188CT polymorphisms with maternal plasma soluble LOX-1 levels and preeclampsia risk in Turkish population.

To investigate the main effect of polymorphisms in genes involved in endothelial pathophysiological mechanisms, LOX-1 K167N and 3'UTR188CT single nucleotide polymorphisms (SNPs) in relation to preeclampsia (PE) risk and possible interactions between the gene polymorphisms and plasma oxLDL and soluble LOX-1 (sLOX-1) levels on PE in Turkish population. LOX-1 K167N and 3'UTR188CT polymorphisms were studied in 113 pregnant women with preeclampsia and 96 healthy pregnant women by the PCR-RFLP techniques. sLOX-1 and oxLDL levels were determined by enzyme-linked immunosorbent assay (ELISA) in all study subjects. Patients having LOX-1 3'UTR188CT (OR 3.55, 95% CI 1.89-6.67, P = 0.001) or 3'UTR188CC (OR 3.04, 95% CI 1.25-7.38, P = 0.012) genotype had a significantly higher risk of PE than those with 3'UTR188TT genotype. Also, patients having K167N KK (OR 2.73, 95% CI 1.33-5.61, P = 0.005) genotype had a significantly higher risk of PE than those with K167N NN genotype. LOX-1 3'UTR188TT and LOX-1 K167N NN genotype carriers were associated with significantly increased serum sLOX-1 level (P = 0.001). We further investigated the potential combined effect of these polymorphic variants on risk of PE development. According to the combined genotype analysis of LOX-1 3'UTR188TT and K167N NN polymorphisms, sLOX-1 and oxLDL levels also showed significant differences between PE patients and controls with or without combined TT/NN genotype carriers. Our findings indicate that higher plasma sLOX-1 and oxLDL concentrations, and the LOX-1 3'UTR188C>T and LOX-1 K167N gene polymorphisms were significantly associated with risk of developing preeclampsia. Plasma sLOX-1 may be a potential therapeutic target in the treatment of preeclampsia.

Associations between CD36 gene polymorphisms and susceptibility to coronary artery heart disease.

Associations between polymorphisms of the CD36 gene and susceptibility to coronary artery heart disease (CHD) are not clear. We assessed allele frequencies and genotype distributions of CD36 gene polymorphisms in 112 CHD patients and 129 control patients using semi-quantitative polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Additionally, we detected CD36 mRNA expression by real-time quantitative PCR, and we quantified plasma levels of oxidized low-density lipoprotein (ox-LDL) using an enzyme-linked immunosorbent assay (ELISA). There were no significant differences between the two groups (P>0.05) in allele frequencies of rs1761667 or in genotype distribution and allele frequencies of rs3173798. The genotype distribution of rs1761667 significantly differed between CHD patients and controls (P=0.034), with a significantly higher frequency of the AG genotype in the CHD group compared to the control group (P=0.011). The plasma levels of ox-LDL in patients with the AG genotype were remarkably higher than those with the GG and AA genotypes (P=0.010). In a randomized sample taken from patients in the two groups, the CD36 mRNA expression of the CHD patients was higher than that of the controls. In CHD patients, the CD36 mRNA expression in AG genotype patients was remarkably higher than in those with an AA genotype (P=0.005). After adjusted logistic regression analysis, the AG genotype of rs1761667 was associated with an increased risk of CHD (OR=2.337, 95% CI=1.336-4.087, P=0.003). In conclusion, the rs1761667 polymorphism may be closely associated with developing CHD in the Chongqing Han population of China, and an AG genotype may be a genetic susceptibility factor for CHD.

OxLDL – the molecule linking hypercoagulability with the presence of cardiovascular disease in hemodialyzed uraemic patients

IntroductionPatients with end-stage renal disease (ESRD) exhibit features of a hypercoagulable state, which may contribute to cardiovascular complications. Data from “in vitro” studies suggest that cell-free plasma lipids and lipoproteins may be capable to support thrombin generation. The aim of this study has been to establish the role of plasma oxidized LDL (oxLDL) in the coagulation activation in hemodialyzed (HD) patients with and without cardiovascular disease (CVD). Materials and MethodsWe examined relationship between a marker of coagulation activation – prothrombin fragments 1+2 (F1+2), and plasma oxLDL levels in 60 HD patients with and without CVD and in 20 healthy controls. ResultsF1+2 levels were significantly higher in HD patients than in controls, and they were higher in HD patients with CVD compared to those without CVD (p<0.001). Conversely, oxLDL levels were similar in HD patients with CVD and healthy controls, whereas this parameter was lower in HD patients without CVD when compared to controls and patients with CVD (both p<0.01). Close positive and independent association was between F1+2 and oxLDL levels in HD patients. Nitrates treatment and the presence of pyelonephritis were associated with reduced oxLDL as well as hypercoagulability in HD patients with cardiovascular complications. ConclusionThis study demonstrates the independent association between oxLDL and the marker of coagulation activation - F1+2 in HD patients. This new observation may offer a better understanding of the complex mechanism leading to hypercoagulability, which is markedly intensified in these patients, particularly in those with CVD.

Comparison of maternal and umbilical cord blood soluble lectin-like oxidized low-density lipoprotein receptor 1 levels in early- and late-onset preeclampsia

The main purpose of this study was to determine the maternal and umbilical cord blood oxidized LDL (oxLDL) and soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) levels in early- and late-onset preeclampsia (PE). A case-control study was conducted in pregnant women with early-onset (before 34 weeks' gestation n = 19) and late-onset (after 34 weeks' gestation n = 22) PE compared to healthy normotensive pregnant controls (n = 44). Groups were compared for the maternal and umbilical cord plasma oxLDL and serum sLOX-1 levels. The mean maternal and umbilical cord serum sLOX-1 and plasma oxLDL levels were significantly increased in early- and late-onset PE compared to controls (p < 0.001). When early- and late-onset PE women were compared with serum sLOX-1 levels, the increase was more pronounced in early PE (p < 0.001). However, same comparison is not statistically significant in cord blood for oxLDL where as it is significantly higher in maternal blood for oxLDL in early-onset PE group. Maternal and cord blood oxLDL and sLOX-1 levels are positively correlated with each other; however, they are negatively correlated with fetal weight and gestational age. According to our results, maternal and umbilical cord blood levels of oxLDL and sLOX-1 were higher in preeclamptic pregnant. Thus, for the first time it has been shown that oxLDL and sLOX-1 levels were higher in fetal circulation as well as plasma of preeclamptic pregnant. However, sLOX-1 levels seem to be more implying than oxLDL for the differentiation of early and late preeclampsia.

Abstract 77: Endothelial LOX-1 Protects Against Arterial Thrombosis via Activation of the Oct-1/SIRT1 Pathway

Background: The lectin-like oxLDL receptor-1 (LOX-1) promotes the endothelial uptake of oxidized low-density lipoprotein (oxLDL). However, LOX-1 is involved in several other biological processes and its role in arterial thrombus formation remains unknown. The present study was designed to investigate whether LOX-1 activation plays a role in thrombus formation in vivo. Methods and Results: Endothelial-specific LOX-1 transgenic mice were generated using the Tie2 promoter (LOX-1TG). While plasma levels of oxLDL were comparable, carotid tissue oxLDL content was markedly increased in LOX-1TG as compared to wild type (WT). Arterial thrombus formation was assessed using an in vivo photochemical injury model. Time to arterial occlusion was prolonged in LOX-1TG as compared to WT. In line with this, tissue factor (TF) expression and activity were reduced by 50% in the carotid arteries of LOX-1TG mice. This effect was mediated by the activation of the transcription factor Oct-1 leading to upregulation of mammalian deacetylase SIRT1 via binding to its promoter and subsequent inhibition of NF-κB signaling as demonstrated by siRNA experiments. This was further confirmed in LOX-1TG endothelial cells (EC) where expression of Oct-1 and SIRT1 was increased upon exposure to oxLDL. Increased expression of SIRT1 was further associated with decreased DNA-binding of RelA/p65 subunit of NF-κB. Conclusions: LOX-1 activates a novel compensatory pathway which protects against arterial thrombus formation in vivo. These unexpected findings suggest that Oct-1/SIRT1 signaling may represent a novel target for the prevention of arterial thrombus formation in the setting of hyperlipidemia and atherosclerosis.

Influence of abdominal obesity on circulating oxidative and inflammatory markers in overweight/obese adult men (1107.7)

The aim of this study was to determine whether overweight/obese adults with abdominal adiposity exhibit greater oxidative stress and inflammatory burden compared with overweight/obese adults without abdominal obesity. 38 sedentary, adult males free of cardiometabolic disease were studied: 12 normal weight (age 54±2 yr; BMI 22.4±0.6 kg/m2; waist circumference [WC] 82.9+1.4 cm); 15 overweight/obese with WC &lt;102 cm (58+2 yr; 28.1+0.3 kg/m2; 95.5+0.8 cm); and 11 overweight/obese with WC &gt;102 cm (58+3 yr; 29.8+0.7 kg/m2; 107.9+1.7 cm). Plasma concentrations of oxidized low‐density lipoprotein (ox‐LDL), C‐reactive protein (CRP), tumor necrosis factor (TNF)‐α, interleukin (IL)‐6 and IL‐18 were determined by ELISA. Plasma oxLDL (48.7±2.3 U/L), CRP (0.4±0.1 mg/L), TNF‐α (1.5±0.1 pg/mL), IL‐6 (1.3±0.2 pg/mL) and IL‐18 (214±12 pg/mL) levels were lowest in normal weight controls. Importantly, overweight/obese men with abdominal adiposity had significantly higher CRP (2.5±0.7 vs 1.1±0.2 mg/L), IL‐6 (2.9±0.7 vs 1.5±0.3 pg/mL) and IL‐18 (292±15 vs 228±16 pg/mL) levels than overweight/obese adults without abdominal adiposity. There were no group differences in either ox‐LDL (58.4±7.5 vs 55.0±6.0 U/L) or TNF‐α (2.1±0.2 vs 2.6±0.6 pg/mL) amongst the overweight/obese men. These results suggest that abdominal obesity is associated with a more unfavorable inflammatory phenotype in overweight/obese men.

Assessment of Small C-Fiber Status for Screening of Oxidative Stress in Patients at Risk of Diabetes

Oxidized LDL (oxLDL), anti-oxLDL antibody (anti-oxLDL) and paraoxonase (PON1) are increasingly being reported to be associated with diabetic atherosclerosis. Oxidative stress could affect also small C-fibers innervating the sweat glands even in prediabetes. Hence it could be hypothesized that sweat dysfunction may be a predictor of oxidative stress status for early detection of diabetes. Ezscan, a new device, has recently been developed to measure the sweat function. Therefore, this study was aimed to determine the relevance of this Ezscan method to identify impairment in oxidative stress parameters. Plasma levels of oxLDL and anti-oxLDL were measured by enzyme immunoassay and ELISA respectively. Small C-fiber status was assessed by measurement of hand and foot sweat function with the help of Ezscan device and subsequent calculation of a risk score. Out of 82 subjects recruited in this study, 38 had impaired glucose tolerance and 6 had newly diagnosed diabetes mellitus. Ezscan risk score was significantly (p=0.004) correlated with oxLDL/anti-oxLDL ratio (0.32). Area under the curve (AUC) of receiver operating characteristics (ROC) analysis for detection of oxLDL/anti-oxLDL ratio (>0.12) was 0.76. For an Ezscan risk score of 50%, the sensitivity and specificity were 68% and 71% respectively. After adjustment for age and BMI, PON1 activity showed significant difference among the 3 risk groups defined by Ezscan risk score. Based on these results it may be concluded that Ezscan could be a useful screening tool in daily practice to assess alterations in oxidative stress parameters in individuals at risk of developing diabetes.

Absence of clinical relationship between oxidized low density lipoproteins and diabetic peripheral neuropathy: a case control study

BackgroundThe pathophysiology of diabetic peripheral neuropathy (DPN) is complex and uncertain. A potential comorbidity in diabetes mellitus (DM) that may contribute to greater severity of DPN is a lipid disorder, such as with elevated cholesterol, low density lipoproteins or triglycerides. Oxidized low density lipoprotein (oxLDL) is a form of cholesterol that exerts direct toxic effects and contributes to pathogenicity through ligating a receptor called lectin-like receptor (LOX-1).MethodsWe examined plasma oxLDL levels in cohorts of patients with DPN with neuropathic pain (NeP), DPN patients without NeP, DM patients without DPN, patients with idiopathic peripheral neuropathy, and control subjects without DM or neuropathy. Our outcome measure was extent of oxLDL elevation, measured as fasting with Enzyme-Linked ImmunoSorbant Assay (ELISA) studies. Severity of diabetes was assessed using hemoglobin A1C measurements. Neuropathic severity was measured with the Utah Early Neuropathy Score (UENS). We hypothesized that DPN presence would be associated with oxLDL elevations.ResultsA total of 115 subjects (47 with DPN and NeP, 23 with DPN without NeP, 12 with diabetes only, 13 with idiopathic peripheral neuropathy, and 20 control subjects without diabetes or neuropathy) were studied. Duration of diabetes and diabetic glycemic measures were similar between populations with DM. Severity of DPN was similar between cohorts with DPN and NeP and DPN without NeP. Plasma oxLDL levels were similar between all cohorts, without any elevation in the presence of DM noted in any cohort with DM.ConclusionsoxLDL levels are not different in patients with DPN, and their lack of greater presence suggests that any pathogenic role in human DPN is likely limited.