sLOX-1 Levels Research Articles

SLOX-1: A Molecule for Evaluating the Prognosis of Recurrent Ischemic Stroke.

Several clinical parameters and biomarkers have been proposed as prognostic markers for stroke. However, it has not been clarified whether the risk factors affecting the prognosis of patients with recurrent and first-ever stroke are similar. In this study, we aimed to explore the relationship between soluble lectin-like oxidized low-density lipoprotein receptor 1 (sLOX-1) levels and the prediction of the functional outcome in patients with recurrent and first-ever stroke. A total of 266 patients with recurrent and first-ever stroke, who underwent follow-up for 3 months, were included in this study. Plasma samples were collected within 24 h after onset. The results showed that biomarkers for the prognosis of patients with recurrent stroke were different from that of those with first-ever stroke. sLOX-1 levels were correlated with modified Rankin Scale scores of patients with recurrent stroke alone (r = 0.3232, p = 0.001). sLOX-1 levels were also associated with an increased risk of unfavorable outcomes in patients with recurrent stroke with an adjusted odds ratio of 1.489 (95% confidence interval, 1.204–1.842, p < 0.0001). Combining the risk factors showed greater accuracy for prognosis, yielding a sensitivity of 93.2% and a specificity of 75%, with an area under the curve of 0.916, evaluated by the receiver operating characteristic curve. These findings suggest that the diagnosis and prognosis are different between patients with recurrent stroke and those with first-ever stroke, and sLOX-1 level is an independent prognostic marker in patients with recurrent stroke.

Short-term exposure to air pollution and biomarkers of cardiovascular effect: A repeated measures study.

To help understand the pathophysiologic mechanisms linking air pollutants and cardiovascular disease (CVD), we employed a repeated measures design to investigate the associations of four short-term air pollution exposures - particulate matter less than 2.5μm in diameter (PM2.5), nitrogen dioxide (NO2), ozone (O3) and sulfur dioxide (SO2), with two blood markers involved in vascular effects of oxidative stress, soluble lectin-like oxidized LDL receptor-1 (sLOX-1) and nitrite, using data from the Multi-Ethnic Study of Atherosclerosis (MESA). Seven hundred and forty participants with plasma sLOX-1 and nitrite measurements at three exams between 2002 and 2007 were included. Daily PM2.5, NO2, O3 and SO2 zero to seven days prior to blood draw were estimated from central monitors in six MESA regions, pre-adjusted using site-specific splines of meteorology and temporal trends, and an indicator for day of the week. Unconstrained distributed lag generalized estimating equations were used to estimate net effects over eight days with adjustment for sociodemographic and behavioral factors. The results showed that higher short-term concentrations of PM2.5, but not other pollutants, were associated with increased sLOX-1 analyzed both as a continuous outcome (percent change per interquartile increase: 16.36%, 95%CI: 0.1-35.26%) and dichotomized at the median (odds ratio per interquartile increase: 1.21, 95%CI: 1.01-1.44). The findings were not meaningfully changed after adjustment for additional covariates or in several sensitivity analyses. Pollutant concentrations were not associated with nitrite levels. This study extends earlier experimental findings of increased sLOX-1 levels following PM inhalation to a much larger population and at ambient concentrations. In light of its known mechanistic role in promoting vascular disease, sLOX-1 may be a suitable translational biomarker linking air pollutant exposures and cardiovascular outcomes.

Soluble Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Level is Related to Clinical Prognosis In Patients with Acute Atherosclerosis-related Ischemic Stroke.

To investigate the associations between soluble Lectin-like Oxidized Low-density lipoprotein receptor-1 (sLOX-1) and clinical prognosis, especially infarct volume in patients with acute atherosclerosis-related ischemic stroke. We recruited acute ischemic stroke patients within 3 days after onset. Patients were stratified into 3 groups by sLOX-1 level. Initial stroke severity was assessed using the National Institutes of Health Stroke Scale scores, and infarct volume was measured using DWI by ITK-SNAP software. The clinical prognosis was evaluated by DWI volume, clinical response at discharge, and functional outcome at 90 days. Spearman rank correlation analysis was used to examine associations between circulating sLOX-1 levels and infarct volumes. Logistic regression was used to explore the relationship between sLOX-1 levels and clinical prognosis. A total of 207 patients were included in our study. The median DWI volume in the lowest sLOX-1 tertile was 1.98 cm3, smaller than 4.26 cm3 in the highest sLOX-1 group. The Spearman rank correlation coefficient between sLOX-1 levels and DWI volume was 0.47 (P < .01). Compared with the highest sLOX-1 tertiles, patients in the lowest sLOX-1 tertile had a higher risk of favorable functional outcome at 90 days (OR = 3.47, 95% CI, 1.21-9.96) after adjusting traditional risk factors. However, there was no difference between sLOX-1 level and clinical response at discharge. For patients with acute atherosclerosis-related ischemic stroke, circulating sLOX-1 level is correlated with DWI volume in the acute phase and favorable functional outcome at 90 days, but not with the clinical response at discharge.

Reduced oxidized LDL in T2D plaques is associated with a greater statin usage but not with future cardiovascular events

BackgroundType 2 diabetes (T2D) patients are at a greater risk of cardiovascular events due to aggravated atherosclerosis. Oxidized LDL (oxLDL) has been shown to be increased in T2D plaques and suggested to contribute to plaque ruptures. Despite intensified statin treatment during the last decade the higher risk for events remains. Here, we explored if intensified statin treatment was associated with reduced oxLDL in T2D plaques and if oxLDL predicts cardiovascular events, to elucidate whether further plaque oxLDL reduction would be a promising therapeutic target.MethodsCarotid plaque OxLDL levels and plasma lipoproteins were assessed in 200 patients. Plaque oxLDL was located by immunohistochemistry. Plaque cytokines, cells and scavenger receptor gene expression were quantified by Luminex, immunohistochemistry and RNA sequencing, respectively. Clinical information and events during follow-up were obtained from national registers.ResultsPlaque oxLDL levels correlated with markers of inflammatory activity, endothelial activation and plasma LDL cholesterol (r = 0.22-0.32 and p ≤ 0.01 for all). T2D individuals exhibited lower plaque levels of oxLDL, sLOX-1(a marker of endothelial activation) and plasma LDL cholesterol (p = 0.001, p = 0.006 and p = 0.009). No increased gene expression of scavenger receptors was identified in T2D plaques. The lower oxLDL content in T2D plaques was associated with a greater statin usage (p = 0.026). Supporting this, a linear regression model showed that statin treatment was the factor with the strongest association to plaque oxLDL and plasma LDL cholesterol (p < 0.001 for both). However, patients with T2D more frequently suffered from symptoms and yet plaque levels of oxLDL did not predict cardiovascular events in T2D (findings are summarized in Fig. 1a).ConclusionsThis study points out the importance of statin treatment in affecting plaque biology in T2D. It also implies that other biological components, beyond oxLDL, need to be identified and targeted to further reduce the risk of events among T2D patients receiving statin treatment.

Identification of plaque ruptures using a novel discriminative model comprising biomarkers in patients with acute coronary syndrome

Soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1), neutrophil gelatinase-associated lipocalin (NGAL), and matrix metalloproteinase-9 (MMP-9) are inflammatory biomarkers involved in plaque destabilization resulting in acute coronary syndrome (ACS). This study aimed to investigate the diagnostic value of a combination of biomarkers to discriminate plaque ruptures in the setting of ACS. Eighty-five ACS patients with optical coherence tomography (OCT) images of the culprit plaque were included and categorized into two groups: ACS with plaque rupture (Rupture group, n = 42) or without plaque rupture (Non-rupture group, n = 43) verified by OCT. A discriminative model of plaque rupture using several biomarkers was developed and validated. The Rupture group had higher white blood cell (WBC) counts and peak creatine kinase-myocardial band (CK-MB) levels (13.39 vs. 2.69 ng/mL, p = 0.0016). sLOX-1 (227.9 vs. 51.7 pg/mL, p < 0.0001) and MMP-9 (13.4 vs. 6.45 ng/mL, p = 0.0313) levels were significantly higher in the Rupture group, whereas NGAL showed a trend without statistical significance (59.03 vs. 53.80 ng/mL, p = 0.093). Receiver operating characteristic curves to differentiate Rupture group from Non-rupture group calculated the area under the curve for sLOX-1 (p < 0.001), MMP-9 (p = 0.0274), and NGAL (p = 0.0874) as 0.763, 0.645, and 0.609, respectively. A new combinatorial discriminative model including sLOX-1, MMP-9, WBC count, and the peak CK-MB level showed an area under the curve of 0.8431 (p < 0.001). With a cut-off point of 0.614, the sensitivity and specificity of plaque rupture were 62.2% and 97.6%, respectively. The new discriminative model using sLOX-1, MMP-9, WBC count, and peak CK-MB levels could better identify plaque rupture than each individual biomarker in ACS patients.

The clinical impact of serum sLOX-1 level in coronary artery disease patients as inferred from its implication in the in vitro protective effects of metoprolol against hypoxic injury of HUVECs

Abstract Background Ischemic coronary artery disease (CAD) is a major public health problem across the world. Early detection and appropriate management significantly reduced CAD-induced morbidities and death. Endothelial cells are pathogenically implicated. Purpose Our study was designed to investigate the role of the soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) in the in vitro protective effect of Metoprolol against hypoxia-induced injury of Human umbilical vein endothelial cells (HUVECs). Secondly, the clinical significance of variations in serum levels of sLOX-1 in patients with CAD was assessed. Methods In vitro, hypoxic injury model of HUVECs was established in an atmosphere of 1% O2, 95% N2, and 5% CO2 for 24 hours. The protective effect and mechanism of action of the cardio-selective beta-blocker Metoprolol at 10–6 μM concentration was investigated. Consented stable atherosclerotic CAD (n=150) and unstable angina pectoris patients (n=75) along with 150 healthy volunteer subjects were voluntarily enrolled in this ethically approved study. Invasive coronary angiogram with ≥50% stenosis at least in one major coronary artery was used for diagnosis. ESC/ACC/AHC/practical protocols were used for categorizing patients into stable or unstable CAD. Serum sLOX-1 level was measured using specific ELISA kit. The diagnostic significance of serum sLOX-1 levels was assessed by analyzing its area under the curve (AUC). Results In vitro hypoxic conditions induced high rate of cellular apoptosis, high levels of LOX-1 expression, reactive oxygen species (ROS) generation and LDH release from HUVECs after 24 hours incubation, compared to normoxic control cells. Metoprolol significantly decreased LOX-1 levels, and prevented the release of LDH and generation of ROS. This culminated into marked improvement in cellular viability of hypoxia-exposed HUVECs (p&amp;lt;0.001). Compared to healthy subjects, serum levels of sLOX-1s were significantly elevated in atherosclerotic stable and unstable CAD patients (p&amp;lt;0.001). Serum sLOX-1 levels were increased by 4.21 folds in stable CAD patients and by 6.373 folds in atherosclerotic unstable angina patients vs. healthy participants. Moreover, the levels in the two patients' groups were significantly different (p&amp;lt;0.001). In stable angina CAD patients, sLOX-1 AUC = 0.929; and in unstable CAD patients, AUC = 0.944, indicating that serum sLOX-1 levels clearly differentiated patients from healthy participants with high specificity and sensitivity. Conclusions Extrapolated from HUVECs hypoxia-induced injury model and the protective effect of Metoprolol, elevation of the circulating levels of sLOX-1 correlated with increased risks for atherosclerotic CAD and is a highly sensitive and specific biomarker for early detection of the disease. Funding Acknowledgement Type of funding source: None

Short-term exposure to air pollution and novel markers of cardiovascular effect: a repeated measures study in the Multi-Ethnic Study of Atherosclerosis (MESA)

Background: Several pathophysiologic mechanisms have been proposed to underlie the associations between ambient air pollutants and cardiovascular disease. We employed a repeated measures design to investigate the short-term associations of outdoor concentrations of four air pollutants – particulate matter smaller than 2.5 micrometers in diameter (PM2.5), nitrogen dioxide (NO2), ozone (O3) and sulfur dioxide (SO2) – with two blood markers involved in vascular effects of oxidative stress, soluble lectin-like oxidized LDL receptor-1 (sLOX-1) and nitrite, using data from the MESA study.Methods: 740 participants who submitted blood samples at three MESA exams between 2002 and 2007 were included. sLOX-1 and nitrite were measured in plasma samples. Daily concentrations of PM2.5, NO2, O3 and SO2 0-7 days prior to blood draw at each exam were estimated from central monitors in the six MESA regions, pre-adjusted using splines of meteorology, indicators for day of the week, and splines of site-specific time trend. Unconstrained distributed lag linear mixed effect models and generalized estimating equations were used to estimate net effects over several days with adjustment for demographic, socioeconomic and behavioral factors.Results: Median detectable nitrite and sLOX-1 concentrations were 24.7 umol/L and 94.5 pg/ml, respectively. Higher short-term PM2.5 concentrations, but not other pollutants, were associated with elevated sLOX-1 level analyzed both as a continuous outcome (percent change per interquartile increase: 18.5%, 95%CI: 2.4-37.2%) and dichotomized at the median (odds ratio per interquartile increase: 1.21, 95%CI: 1.01-1.44); the finding was not meaningfully changed after adjustment for additional covariates or in several sensitivity analyses. Pollutant concentrations were not associated with nitrite levels. Conclusion: This study adds to the evidence that short-term PM2.5 exposure is associated with higher sLOX-1 and supports the mechanistic hypothesis that oxidative modification of endogenous phospholipids in the lung by PM2.5 drives vascular endothelial cell activation via cell surface pattern recognition receptors.

Role of Plasma Soluble Lectin Like Oxidized Low-Density Lipoprotein Receptor-1 in Severity of CAD Patients and Relationship with Microrna-98

Coronary artery diseases are the most important cause of premature death and it is predominantly related to atherosclerosis. Soluble lectin like oxidized low-density lipoprotein receptor-1 (sLOX-1) and microRNAs are closely associated with atherosclerotic coronary heart diseases. The current study investigated the relationship of plasma slOX-1and the severity of coronary artery disease patients (CAD) and association with microRNA-98. Case control study. Angiographically documented 38 single coronary lesions, 75 double coronary artery disease, 62 multi-vessel coronary artery disease patients, 62 healthy control subjects, and 24h hypoxic (1% O2) HUVEC cells were included in this study. Circulating sLOX-1concentrations were determined through enzyme-linked immunosorbent assays and microRNA-98 expressions were measured by the quantitative real- time polymerase chain reaction. The expressions of plasma sLOX-1 levels were progressively and significantly higher in single, double, and multi-vessel CAD patients than healthy control subjects (p<0.001). Circulating sLOX-1 concentrations in multi-vessel, double vessel and single vessel CAD female subjects had evidently elevated than male subjects (p<0.001). Plasma sLOX-1 values were remarkably increased in female different age groups CAD patients as compared with the same male age subjects (p<0.001). Single vessel diseased (AUC 0.879), double vessel diseased (AUC 0.928) and multi-vessel diseased (AUC 0.943) CAD patients have been clearly differentiated from healthy participants with high sensitivity and specificity. The expression of microRNA-98 noticeably down-regulated in single, double and multi-vessel occluded CAD patients and hypoxic exposed HUVEC than controls (p<0.001). Significantly elevated LOX-1 and caspase-3 activity and remarkably decreased cellular viability in hypoxic injured HUVEC. On the contrary, mimic of microRNA-98 markedly reduced caspase-3 and LOX-1 levels and highly increased cellular viability. Elevated circulating plasma sLOX-1 levels have a potential impact to identify the severity of coronary artery disease and a strong correlation with aging as well as the female gender. Reduced plasma miR-98 level possible considers a risk factor for CAD, and agomiR-98 prevents atherosclerosis and cellular injury through targeting LOX-1.

Polycystic ovary syndrome and endothelial dysfunction: A potential role for soluble lectin-like oxidized low density lipoprotein receptor-1

The aims of this study were to investigate whether serum soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1), oxidized LDL (oxLDL), paraoxonase-1(PON-1) and hydroperoxide (LOOH) levels are altered in women with polycystic ovary syndrome (PCOS) and also to determine if hyperandrogenism, insulin resistance (IR) and Anti-Müllerian Hormone (AMH) are associated with endothelial dysfunction in PCOS. A total of 46 women with PCOS and 46 non-PCOS healthy controls were recruited. Women with PCOS had significantly higher sLOX-1, oxLDL and LOOH concentrations than non-PCOS women [6.16 (3.92−13.95) vs 1.37 (0.63−4.43) ng/mL, p < 0.001; 6.48 ± 1.03 vs 3.16 ± 1.02 μU/L, p < 0.001; 2.45 (1.45−3.45) vs 1.06 (0.64−1.56) μmol/L, p < 0.001]. The mean PON-1 level of PCOS group was lower than non-PCOS group (69.47 ± 10.75 vs 104.08 ± 21.43 U/mL, p < 0.001). There was no significant difference in terms of the sLOX-1, oxLDL, LOOH and PON-1 levels between normal weight and overweight PCOS women. On univariate logistic regression analysis, Ferriman-Gallwey scale (FGS), HOMA-IR and AMH were an independent predictors of high risk group of endothelial dysfunction markers (HR-EDm). Age and BMI were not associated with HR-EDm. When incorporated into the multivariate model, endotelial dysfunction markers independently correlated with clinical hyperandrogenism (FGS) but not with AMH. In conclusion, our results indicated that an increased concentration of sLOX-1 might be an early predictor of endothelial damage in patients with PCOS. Women with PCOS have elevated sLOX-1, oxLDL, LOOH and decreased PON-1 levels, independent of BMI. Endothelial dysfunction in women with PCOS is associated with hyperandrogenism. Further studies are required to confirm our findings.

LOX-1: A potential driver of cardiovascular risk in SLE patients.

Traditional cardiovascular disease (CVD) risk factors, such as hypertension, dyslipidemia and diabetes do not explain the increased CVD burden in systemic lupus erythematosus (SLE). The oxidized-LDL receptor, LOX-1, is an inflammation-induced receptor implicated in atherosclerotic plaque formation in acute coronary syndrome, and here we evaluated its role in SLE-associated CVD. SLE patients have increased sLOX-1 levels which were associated with elevated proinflammatory HDL, oxLDL and hsCRP. Interestingly, increased sLOX-1 levels were associated with patients with early disease onset, low disease activity, increased IL-8, and normal complement and hematological measures. LOX-1 was increased on patient-derived monocytes and low-density granulocytes, and activation with oxLDL and immune-complexes increased membrane LOX-1, TACE activity, sLOX-1 release, proinflammatory cytokine production by monocytes, and triggered the formation of neutrophil extracellular traps which can promote vascular injury. In conclusion, perturbations in the lipid content in SLE patients’ blood activate LOX-1 and promote inflammatory responses. Increased sLOX-1 levels may be an indicator of high CVD risk, and blockade of LOX-1 may provide a therapeutic opportunity for ameliorating atherosclerosis in SLE patients.

Association between impaired cutaneous microvascular endothelial function and lectin-like oxidized low-density lipoprotein receptor-1 in patients with coronary slow flow

ObjectiveAlthough increasing studies indicate coronary slow flow (CSF) is a systemic microvascular disorder, whether there is impaired cutaneous microvascular endothelial function in CSF patients remains unclear. This study was designed to test the hypothesis that the cutaneous microvascular endothelial function of CSF patients is impaired and correlates with lectin-like oxidized low-density lipoprotein receptor-1(LOX-1). Methods39 patients with CSF and 45 controls with normal coronary flow were enrolled. Velocity of coronary flow was quantitatively identified by thrombolysis in myocardial infarction frame count (TFC) method. LSCI system was used to assess subjects' cutaneous blood flow at rest and during PORH. Serum soluble LOX-1(sLOX-1) level was measured in all study subjects. ResultsPORH-induced vasodilation was significantly reduced in CSF group in comparison with control group (0.26 ± 0.10 vs 0.35 ± 0.07 APU/mmHg, P < 0.001) and negatively correlated with the mean TFC for three coronary arteries (r = −0.385, P = 0.016). Serum sLOX-1 level in CSF group was significantly increased (582.93 ± 74.89 vs 483.64 ± 51.38 pg/ml, P < 0.001) and positively correlated with mean TFC(r = 0.467, P = 0.003).PORH response amplitudes had a significantly negative relationship with serum sLOX-1 level in CSF patients (r = −0.588, P < 0.001). ConclusionThese data suggest that cutaneous microvascular endothelial function is impaired in patients with CSF, which is closely associated with increased LOX-1 expression.

Evaluation of hs-CRP and sLOX-1 Levels in Moderate-to-High Risk Acute Coronary Syndromes.

Risk stratification and prompt treatment are essential for the management of acute coronary syndromes (ACS) and prediction of future prognosis. Subclinical vascular inflammation and novel biomarkers play an important role in the clinical evaluation of ACS patients. We enrolled patients who were admitted to emergency service with unstable angina or non- ST segment elevated ACS (NSTE-ACS) in the study population. Coronary artery disease (CAD) complexity was determined via evaluation of angiographical views and peripheral venous blood samples were collected to measure highly sensitive C-reactive protein (hs-CRP) and soluble form of Lectin-like OxLDL receptor-1 (sLOX-1) levels. A total of 40 patients were enrolled in the study population, mean age was 65.1±13.8 years and male gender percentage was 52.5%. Twenty-nine of patients had NSTE-ACS and 11 patients had unstable angina presentation. The modified Gensini scores were higher for patients with elevated hs- CRP and sLOX-1 levels. Vascular inflammation displays the onset of ACS and it is related to more complex CAD in these patients. An increase in sLOX-1 expression is closely related to anatomical complexity of CAD in ACS.

Soluble Lectin-Like Oxidized Low-Density Lipoprotein Receptor 1 Is Inversely Correlated with the Activity of ANCA-Associated Vasculitis.

Lectin-like oxidized low-density lipoprotein (LDL) receptor 1 (LOX1) binds to oxidized LDL, which is associated with inflammation in various vascular disorders. Here, we aimed to investigate the potential of soluble LOX1 (sLOX1) as an indicator of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) activity. Serum levels of sLOX1 in frozen samples from patients with AAV enrolled in a prospective observational cohort study at the Severance Hospital were measured using enzyme-linked immunosorbent assay. Clinical and laboratory data were collected on the date when the blood sampling was performed. The association between sLOX1 and clinical and laboratory data was assessed using Pearson's correlation analysis. The median age of the recruited 79 patients was 62.0 years, and 27 (34.2%) patients were men. The median Birmingham vasculitis activity score (BVAS), five-factor score, vasculitis damage index, and sLOX1 level were 6, 1, 3, and 911.9 pg/mL, respectively. Correlation analysis based on BVAS revealed that sLOX1 and total cholesterol were significantly inversely correlated with BVAS (r=−0.224, p=0.047 and r=−0.424, p<0.001, respectively). No significant correlations were observed between continuous variables and sLOX1 except for BVAS, although total cholesterol tended to correlate with sLOX1 (r=0.190, p=0.093). Additionally, sLOX1 was not influenced by sex, hypertension, diabetes mellitus, or the presence of pulmonary, cardiovascular, and renal involvement of AAV. In summary, sLOX1 was inversely correlated with BVAS in AAV patients, which is different from other vascular diseases or inflammatory diseases.

Association Between Soluble Lectinlike Oxidized Low-Density Lipoprotein Receptor-1 and Coronary Artery Disease in Psoriasis

Psoriasis, a chronic inflammatory skin disease associated with accelerated noncalcified coronary burden (NCB) by coronary computed tomography angiography (CCTA), accelerates lipoprotein oxidation in the form of oxidized modified lipoproteins. A transmembrane scavenger receptor for these oxidized modified lipoproteins is lectinlike oxidized low-density lipoprotein receptor-1 (LOX-1), which has been reported to be associated with coronary artery disease. It is unknown whether this receptor is associated with coronary artery disease in psoriasis. To assess the association between soluble LOX-1 (sLOX-1) and NCB in psoriasis over time. In a cohort study at the National Institutes of Health, 175 consecutive patients with psoriasis were referred from outpatient dermatology practices between January 1, 2013, and October 1, 2017. A total of 138 consecutively recruited patients with psoriasis were followed up at 1 year. Circulating soluble lectinlike oxidized low-density lipoprotein receptor-1 levels were measured blindly by field scientists running undiluted serum using an enzyme-linked immunosorbent assay. Coronary computed tomography angiography scans were performed to quantify NCB in all 3 major epicardial coronary arteries by a reader blinded to patient demographics, visit, and treatment status. Among the 175 patients with psoriasis, the mean (SD) age was 49.7 (12.6) years and 91 were men (55%). The cohort had relatively low median cardiovascular risk by Framingham risk score (median, 2.0 [interquartile range (IQR), 1.0-6.0]) and had a mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) suggestive of overweight profiles (29.6 [6.0]). Elevated sLOX-1 levels were found in patients with psoriasis compared with age- and sex-matched controls (median, 210.3 [IQR, 110.9-336.2] vs 83.7 [IQR, 40.1-151.0]; P < .001), and were associated with Psoriasis Area Severity Index (PASI) score (β = 0.23; 95% CI, 0.082-0.374; P = .003). Moreover, sLOX-1 was associated with NCB independent of hyperlipidemia status (β = 0.11; 95% CI, 0.016-0.200; P = .023), an association which persisted after adjusting for traditional cardiovascular risk factors, statin use, and biologic psoriasis treatment (β = 0.10; 95% CI, 0.014-0.193; P = .03). At 1 year, in those who had clinical improvement in PASI (eg, >50% improvement), a reduction in sLOX-1 (median, 311.1 [IQR, 160.0-648.8] vs median, 224.2 [IQR, 149.1 - 427.4]; P = .01) was associated with a reduction in NCB (β = 0.14; 95% CI, 0.028-0.246; P = .02). Soluble lectinlike oxidized low-density lipoprotein receptor-1 levels were elevated in patients with psoriasis and were associated with severity of skin disease. Moreover, sLOX-1 associated with NCB independent of hyperlipidemia status, suggesting that inflammatory sLOX-1 induction may modulate lipid-rich NCB in psoriasis. Improvement of skin disease was associated with a reduction of sLOX-1 at 1 year, demonstrating the potential role of sLOX-1 in inflammatory atherogenesis in psoriasis.

Serum Levels of Carbamylated LDL, Nitrotyrosine and Soluble Lectin-like Oxidized Low-density Lipoprotein Receptor-1 in Poorly Controlled Type 2 Diabetes Mellitus.

Carbamylated low-density lipoprotein (cLDL) has profound proatherogenic properties. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) has been identified as the primary cLDL receptor. The soluble form of LOX-1 (sLOX-1) and 3-nitrotyrosine (NT) have recently been suggested as biomarkers of vascular disease. Although type 2 diabetes mellitus (T2DM) is characterised by an increased atherosclerotic risk, the clinical data on cLDL, NT and sLOX-1 levels in T2DM are limited. To explore the possible role of cLDL, NT and sLOX-1 as potential biomarkers for disease progression and complications in poorly controlled T2DM patients with and without microalbuminuria. The serum concentrations of cLDL, NT and sLOX-1 were measured by ELISA in a cross-sectional study of 60 T2DM patients and 35 nondiabetic controls. Both the normoalbuminuric (n = 34) and the microalbuminuric (n = 26) patients had significantly higher serum levels of cLDL and NT than the healthy controls, but sLOX-1 was only elevated in the microalbuminuric subgroup (p < 0.05). Carbamylated LDL correlated positively with NT in the diabetic subjects (rs = 0.266, p = 0.04) while it correlated with urea only in the control group (rs = 0.475, p = 0.004). The serum concentration of sLOX-1 correlated significantly with fasting glucose (rs = 0.441, p < 0.001), HbA1c (rs = 0.328, p = 0.01) and microalbuminuria (rs = 0.272, p = 0.035) in the whole diabetic cohort. The present study highlights the potential of cLDL, NT and sLOX-1 as possible markers of diabetic complications.

Serum Levels of Carbamylated LDL and Soluble Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Are Associated with Coronary Artery Disease in Patients with Metabolic Syndrome.

Background and objectives: Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) has been recognized as the primary receptor for carbamylated low-density lipoproteins (cLDL) and is increasingly being viewed as a critical mediator of vascular inflammation and atherosclerosis. The aim of the current study was to evaluate the possible role of circulating cLDL and soluble LOX-1 (sLOX-1) as potential biomarkers of metabolic syndrome (MetS) as well as of coronary artery disease (CAD) among MetS patients. Materials and Methods: The serum levels of cLDL and sLOX-1 were measured by ELISA in 30 MetS patients without CAD, 30 MetS patients with CAD, and 30 healthy controls. Results: Patients with MetS had significantly higher serum levels of both cLDL and sLOX-1 than the healthy controls but lower in comparison to MetS + CAD subjects. Serum sLOX-1 concentration correlated significantly with fasting glucose (rs = 0.414, p = 0.001) and high-density lipoprotein (HDL)-cholesterol (rs = −0.273, p = 0.035) in the whole MetS cohort, whereas it correlated with cLDL only in the MetS + CAD subgroup (rs = 0.396, p = 0.030). The receiver-operating characteristic (ROC) curves of cLDL and sLOX-1 for MetS diagnosis had area under the curve (AUC) values of 0.761 and 0.692, respectively. AUC values of cLDL and sLOX-1 for CAD diagnosis among MetS patients were 0.811 and 0.739. Elevated serum levels of cLDL and sLOX-1 were associated with a higher risk of MetS development [odds ratio (OR) 24.28, 95% confidence interval (CI): 5.86–104.61, p < 0.001 and OR 4.75; 95% CI: 1.58–14.25, p = 0.009] as well as with presence of CAD among MetS subjects (OR 11.23; 95% CI: 3.10–40.71, p < 0.001 and OR 4.03; 95% CI: 1.73–11.84, p = 0.019, respectively). Conclusions: The present study underscores the potential of cLDL and sLOX-1 as promising biomarkers for diagnosis and risk assessment of MetS and CAD among the MetS population.

Soluble Lectin-like Oxidized Low-Density Lipoprotein Receptor 1 Predicts the Changes of Rheumatoid Factor Titers in Rheumatoid Arthritis.

The aim of this longitudinal study was to examine the clinical significance of soluble lectin-like oxidized low-density lipoprotein receptor 1 (sLOX-1) in patients with rheumatoid arthritis. We gathered demographic and clinical data for a large rheumatoid arthritis cohort at 3 time points. Blood samples were collected at each time point; the number of samples was 282 cases in 2012, 431 cases in 2013, and 500 cases in 2014. Plasma sLOX-1 was measured by enzyme-linked immunosorbent assay. Correlations between sLOX-1 and clinical data were analyzed. Predictive factors associated with changes in sLOX-1 and rheumatoid factor (RF) were analyzed by multivariate linear regression. Plasma sLOX-1 level was significantly correlated with RF titer and other clinical parameters. The longitudinal analyses showed that changes in sLOX-1 were significantly correlated with changes in RF titers and with those at baseline. Multivariate linear regression analysis revealed that changes in RF and baseline RF were predictive factors for changes in sLOX-1. Conversely, the changes in RF were significantly correlated with the changes in sLOX-1 in all years. A stepwise regression analysis showed that the change in sLOX-1 was a predictive factor for the change in RF. The change in sLOX-1 has predictive value for assessing the change in RF, indicating the usefulness of sLOX-1 in clinical practice.

Evaluation of serum level of soluble lectin-like oxidized low-density lipoprotein receptor-1 and its relationship with severity of preeclampsia and birth weight

Background: Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is one of the pattern recognition receptors that plays a critical role in vascular diseases and host immune response, LOX-1 can induce endothelial dysfunction through pathways implicated with oxidative stress and inflammation that ends with vascular lesions. Objective: The objective of the study is to evaluate the serum level of soluble LOX-1 (sLOX-1) in preeclampsia (PE) and normal pregnancy to study its relationship with the severity of PE and birth weight. Materials and Methods: A total of 56 patients with PE were allocated to the study together with 28 healthy pregnant women as normal controls. PE patients divided into 28 mild and 28 severe PE. Levels of serum sLOX-1 were measured by sandwich enzyme-linked immunosorbent assay technique. Results: Results showed a significant increase in the serum sLOX-1 in preeclamptic patients (P

A Pilot Study of Soluble Form of LOX-1 as a Novel Biomarker for Neonatal Hypoxic-Ischemic Encephalopathy

To evaluate the soluble form of lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) as a biomarker of severity staging and prognosis in neonatal hypoxic-ischemic encephalopathy (HIE). We performed an observational study enrolling 27 infants with HIE and 45 control infants of gestational age ≥36 weeks and birth weight ≥1800 g. The HIE criteria were pH ≤7.0 or a base deficit ≥16 mmol/L within 60 minutes after birth, and a 10-minute Apgar score ≤5 or resuscitation time ≥10 minutes. HIE severity was evaluated using modified Sarnat staging. We measured plasma sLOX-1 level and assessed general and neurologic signs at discharge, and classified infants with no neurosensory impairments as intact survival. sLOX-1 level within 6 hours after birth was correlated with the severity of HIE. sLOX-1 differentiated moderate-severe HIE (median, 1017 pg/mL; IQR, 553-1890 pg/mL) from mild HIE (median, 339 pg/mL; IQR, 288-595 pg/mL; P = .007). The sensitivity and specificity of the differentiation with a cutoff value of ≥550 pg/mL were 80.0% and 83.3%, respectively. In 19 infants with therapeutic hypothermia, a sLOX-1 cutoff value of <1000 pg/mL differentiated intact survival (median, 761 pg/mL; IQR, 533-1610 pg/mL) from death or neurosensory impairment (median, 1947 pg/mL; IQR, 1325-2506 pg/mL; P = .019) with 100% specificity and a positive predictive value. sLOX-1 may be a useful biomarker of neonatal HIE for severity staging and outcome prediction. Further investigations will facilitate its clinical use.

GW29-e0532 Clinical significance of circulating soluble lectin-like oxidized low-density lipoprotein receptor-1 level in acute myocardial infarction patients

The purpose of this study was to establish the diagnostic value of soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) level in acute myocardial infarction patients (AMI). 125 acute ST segment elevated myocardial infarction (STEMI) patients, 75 acute non-ST segment elevated