Lectin-like Oxidized Low-density Lipoprotein Receptor-1 Levels Research Articles

Evaluation of soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) and sLOX-1/oxidized LDL ratio as novel biomarkers of acute coronary syndrome.

The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is involved in the pathophysiology of atherosclerosis and acute coronary syndromes (ACS). In patients with acute coronary syndrome, circulating soluble LOX-1 (sLOX-1) levels are dramatically elevated. This study aimed to assess sLOX-1 levels in acute coronary syndromes and determine the ratio of sLOX-1 and oxidative LDL in cases of myocardial infarction and unstable angina pectoris and the ROC curve for this ratio sLOX-1. A case-control study was conducted at the department of chemistry and biochemistry, college of medicine, Al- Nahrain University, Baghdad, Iraq, from September 2020 to January 2021. In a total of 90 subjects (30 patients with myocardial infarction within the first six hours of chest pains, 30 patients with unstable angina pectoris, and 30 healthy donors). The ELISA technique measured concentrations of sLOX-1 and oxidized LDL. In addition, Troponin and highly sensitive C reactive protein were measured by the same technique (Fluorescence immune assay), and lipid profile was measured using the Spectrophotometer technique. The median level of sLOX-1 in MI group was 476.17 pg/ml (90.88-675.4 pg/ml) which was significantly higher than that of UA patients (median=289.1 pg/ml [62.74-585.43 pg/ml]) and controls (median=144.52 pg/ml [79.17-283.83 pg/ml]) with highly significant differences and the median sLOX-1/OX-LDL ratio in patients with MI was 64.6 (range 15.17-100.15) which was significantly higher than either patients with UA (median=37.6 [7.06-88.65]) or controls (median=25.29 [12.7-43.04]). There were elevated levels of sLOX-1 in acute coronary syndromes. The sLOX-1/oxidized LDL ratio also strongly indicated the diagnosis and a discriminatory force on the ROC curve for myocardial infarction.

Endothelin-1 and LOX-1 as Markers of Endothelial Dysfunction in Obstructive Sleep Apnea Patients.

Introduction: The search of biochemical markers of endothelial dysfunction: lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1)—involved in atherosclerotic plaques formation—and endothelin-1 (ET-1)—potent vasoconstrictor-might help in detecting obstructive sleep apnea (OSA) patients at high risk of cardiovascular diseases. Material and Methods: In 71 OSA patients (apnoea/hypopnoea index, AHI 28.2 ± 17.9/hour) and in 21 healthy controls the serum levels of LOX-1 and ET-1 were measured. Results: There were increased levels of ET-1 (1.58 ± 0.65 vs. 1.09 ± 0.38 pg/mL; p < 0.001) but not of LOX-1 in OSA patients as compared with healthy controls. In the patients’ group ET-1 levels negatively correlated with serum LDL levels. LOX-1 levels positively correlated with fasting glucose levels and were higher in the patients with than without diabetes. Neither ET-1 nor LOX-1 correlated with OSA severity. In mild OSA patients, there was a negative correlation between LOX-1 and mean arterial oxygen saturation during sleep. In severe OSA patients, there was a positive correlation between LOX-1 levels and uric acid. Conclusion: There is endothelial dysfunction in OSA patients as indicated by increased serum levels of ET-1 and possibly endothelial dysfunction in diabetic OSA patients as indicated by increased serum levels of LOX-1 and its correlation with fasting glucose levels.

Serum LOX-1 is a novel prognostic biomarker of colorectal cancer.

Colorectal cancer is the third most common cancer worldwide. If biomarkers can be identified in liquid biopsy, diagnosis and treatment can be optimized even when cancerous tissues are not available. The purpose of this study was to identify proteins from liquid biopsy that would be useful as markers of poor prognosis. First, we comprehensively analyzed serum proteins to identify potential biomarkers and focused on serum lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). The relationship between LOX-1 and the prognosis of patients with colorectal cancer has not been reported. Next, we validated this marker using serum samples from 238 patients with colorectal cancer by ELISA and 100 tissue samples by immunohistochemical staining. The optimal cut-off value of serum LOX-1 was 538.7pg/mL according to time-dependent receiver operating characteristics curve analysis. The overall survival of patients with high levels of serum LOX-1 was significantly poorer than that of individuals with low levels of LOX-1 in the training and test datasets. In multivariate analysis for overall survival, serum LOX-1 was an independent prognostic factor identified in liquid biopsy (hazard ratio = 1.729, p = 0.027). The prognosis of patients with high LOX-1 expression in tumor tissues was significantly poorer than that of individuals with low expression (p =0.047 ). Additionally, inflammatory factors such as white blood cell count, C-reactive protein level, neutrophil/lymphocyte ratio, and monocyte/lymphocyte ratio were significantly higher in the group with high serum LOX-1 levels. Serum LOX-1 might be a useful biomarker of poor prognosis in colorectal cancer.

Evaluation of subclinical atherosclerosis in Turkish patients with acne vulgaris receiving systemic isotretinoin.

Studies conducted on isotretinoin have shown that it may indirectly lead to atherosclerosis. The objective of this study was to determine the effect of systemic isotretinoin on subclinical atherosclerosis. The present study included 63 patients with acne vulgaris who had used isotretinoin for 6 months. Glucose, insulin, and homeostatic model assessment of insulin resistance levels; body mass index; waist circumference; blood pressure; lipid profile; and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), high-sensitivity C-reactive protein, and oxidized low-density lipoprotein (Ox-LDL) levels were compared in the patients at the initiation and discontinuation of the treatment. At the discontinuation of the treatment, LOX-1 and Ox-LDL levels showed a significant increase (P < .001 and P = .040, respectively). Differences in waist circumference were positively correlated with an increase in LOX-1 levels (r = .274; P = .030). Isotretinoin causes an increase in the levels of subclinical atherosclerosis markers. Although the present study sample size was small, we believe that caution should be exercised considering the risk of atherosclerosis during isotretinoin use in men with high waist circumference and cardiovascular risk factors; further studies are warranted in this regard.

LOX-1, the Common Therapeutic Target in Hypercholesterolemia: A New Perspective of Antiatherosclerotic Action of Aegeline.

Background Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is the major receptor for oxidized low-density lipoprotein (Ox-LDL) in the aorta of aged rats. Ox-LDL initiates LOX-1 activation in the endothelium of lipid-accumulating sites of both animal and human subjects of hypercholesterolemia. Targeting LOX-1 may provide a novel diagnostic strategy towards hypercholesterolemia and vascular diseases. Hypothesis This study was planned to address whether aegeline (AG) could bind to LOX-1 with a higher affinity and modulate the uptake of Ox-LDL in hypercholesterolemia. Study Design Thirty-six Wistar rats were divided into six groups. The pathology group rats were fed with high-cholesterol diet (HCD) for 45 days, and the treatment group rats were fed with HCD and aegeline/atorvastatin (AV) for the last 30 days. In vivo and in vitro experiments were carried out to assay the markers of atherosclerosis like Ox-LDL and LOX-1 levels. Histopathological examination was performed. Oil Red O staining was carried out in the IC-21 cell line. Docking studies were performed. Results AG administration effectively brought down the lipid levels induced by HCD. The lowered levels of Ox-LDL and LOX-1 in AG-administered rats deem it to be a potent antihypercholesterolemic agent. Compared to AV, AG had a pronounced effect in downregulating the expression of lipids evidenced by Oil Red O staining. AG binds with LOX-1 at a higher affinity validated by docking. Conclusion This study validates AG to be an effective stratagem in bringing down the lipid stress induced by HCD and can be deemed as an antihypercholesterolemic agent.

Clinical analysis of lectin-like oxidized low-density lipoprotein receptor-1 in patients with in-stent restenosis after percutaneous coronary intervention.

In-stent restenosis (ISR) is the most common complication associated with percutaneous coronary intervention (PCI). Although some studies have reported an association between lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and ISR, not enough clinical validation data are available to support this link. Here, we report our cross-sectional study aimed at exploring the feasibility of LOX-1 as a biomarker for the prognostic diagnosis of patients undergoing PCI.Three groups were included: ISR group, including 99 patients with ISR diagnosed with coronary arteriography (CAG) after PCI; lesion group, comprising 87 patients with coronary artery stenosis (<50%) diagnosed with CAG after PCI; and control group, consisting of 96 volunteers with no coronary artery disease. The levels of LOX-1 were measured in each patient by using an enzyme-linked immunosorbent assay, and their general information as well as laboratory parameters were recorded and followed up during a period of 2 years.LOX-1 levels gradually increased after PCI along with the progression of the lesion in the 3 groups. The levels of LOX-1 were significantly higher in the ISR group than in the other 2 groups (P < .001). LOX-1 levels were correlated with the levels of uric acid (UA) (r = 0.289, P = .007), creatinine (CREA) (r = .316, P = .003), and high-density lipoprotein cholesterol (HDL-C) (r = -0.271, P = .012), whereas no statistically significant correlation was detected with the Gensini score (r = 0.157, P = .141). The sensitivity and specificity of LOX-1 were 81.5% and 55.7%, respectively, with the most optimal threshold (5.04 μg/L). The area under curve (AUC) of the receiver operator characteristic (ROC) curve of LOX-1 was 0.720, and LOX-1 had the highest AUC compared with CREA, UA, and HDL-C, both individually and in combination.A high level of LOX-1 in the early period after PCI has a certain predictive power and diagnostic value for ISR. However, the level of LOX-1 is not related to the Gensini score of coronary artery after PCI, and CREA and UA, which are weakly related to LOX-1, have no obvious synergy in the diagnosis of ISR with LOX-1.

The relationship between serum lectin-like oxidized LDL receptor-1 levels and systolic heart failure.

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) appears to be involved in atherosclerotic plaque vulnerability and rupture. In this study, we aimed to evaluate the utility of serum LOX-1 levels in the diagnosis and assessment of left ventricular systolic HF and LOX-1’s relationship with serum pro-brain natriuretic peptide (NT-proBNP). This was a cross-sectional study of all eligible patients admitted to the department of cardiology of the University Hospital between July 2011 and April 2012. Fifty-five patients with a diagnosis of systolic heart failure and 25 patients without systolic HF were enrolled in this study. Serum C-reactive protein, NT-proBNP, and LOX-1 were studied. Serum LOX-1 and NT-proBNP levels were significantly higher in the heart failure group and showed a positive correlation with NT-proBNP and negative correlations with left ventricular ejection fraction (EF). In addition, LOX-1 levels in patients with ischaemic cardiomyopathy were significantly higher, while they were similar in patients with dilated cardiomyopathy compared to control subjects. Our study demonstrates the utility of the serum LOX-1 levels in the diagnosis of left ventricular systolic heart failure. LOX-1 may have a place in the diagnosis of heart failure, in particular in patients with ischaemic cardiomyopathy.

The relationship between serum lectin-like oxidized LDL receptor-1 levels and systolic heart failure

Objectives Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) appears to be involved in atherosclerotic plaque vulnerability and rupture. In this study, we aimed to evaluate the utility of serum LOX-1 levels in the diagnosis and assessment of left ventricular systolic HF and LOX-1’s relationship with serum pro-brain natriuretic peptide (NT-proBNP).Design and settings This was a cross-sectional study of all eligible patients admitted to the department of cardiology of the University Hospital between July 2011 and April 2012.Methods Fifty-five patients with a diagnosis of systolic heart failure and 25 patients without systolic HF were enrolled in this study. Serum C-reactive protein, NT-proBNP, and LOX-1 were studied.Results Serum LOX-1 and NT-proBNP levels were significantly higher in the heart failure group and showed a positive correlation with NT-proBNP and negative correlations with left ventricular ejection fraction (EF). In addition, LOX-1 levels in patients with ischaemic cardiomyopathy were significantly higher, while they were similar in patients with dilated cardiomyopathy compared to control subjects.Conclusion Our study demonstrates the utility of the serum LOX-1 levels in the diagnosis of left ventricular systolic heart failure. LOX-1 may have a place in the diagnosis of heart failure, in particular in patients with ischaemic cardiomyopathy.

Serum sLOX-1 Levels Are Correlated with the Presence and Severity of Obstructive Sleep Apnea.

Inflammation plays a critical role in the development and progression of obstructive sleep apnea (OSA). Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) activation is involved in the pathophysiology of inflammatory process-related disorders. This study aims to investigate whether serum soluble LOX-1 (sLOX-1) levels are associated with the presence and severity of OSA. A total of 137 OSA patients and 78 controls were recruited in this study. Serum sLOX-1 levels were measured by enzyme-linked immunosorbent assay. The severity of OSA was assessed by the apnea-hypopnea index (AHI). OSA patients had significantly higher serum sLOX-1 levels compared with controls. Serum sLOX-1 levels elevated with the increment of OSA severity. sLOX-1 was the independent predictor of OSA. Serum sLOX-1 levels were significantly correlated with AHI and high-sensitivity C-reactive protein levels. Serum sLOX-1 levels were independently correlated with the presence and severity of OSA. These findings revealed that sLOX-1 might function as a potential biomarker for monitoring the development and progression of OSA.

Increased serum soluble lectin-like oxidized low-density lipoprotein receptor-1 levels in patients with biopsy-proven nonalcoholic fatty liver disease.

To analyze the relationship between the serum lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) levels and clinical and histopathological features of biopsy-confirmed nonalcoholic fatty liver disease (NAFLD) patients. Fifty-three consecutive, biopsy-proven NAFLD patients (31 males and 22 females, mean age 42.5 ± 9.6 years) and 26 age- and gender-matched, healthy controls (14 males and 12 females, mean age 39 ± 10.7 years) were included. The patients with NAFLD were consecutive patients who had been admitted to the hepatology outpatient clinic within the last year and had been diagnosed with NAFLD as the result of liver biopsy. The healthy controls were individuals who attended the outpatient clinic for routine health control and had no known chronic illnesses. The histological evaluation was conducted according to the NAFLD activity scoring system recommended by The National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. The serum LOX-1 levels were measured using an ELISA kit (Life Science Inc. USCN. Wuhan, Catalog No. E1859Hu) in both patients and healthy controls. A receiver operating characteristic (ROC) curve analysis was used to identify the optimal cutoff value of LOX-1 and thereby distinguish between patients with nonalcoholic steatohepatitis (NASH) and healthy controls. A P-value < 0.05 was considered statistically significant. NAFLD and healthy control groups were similar in terms of age and sex. NAFLD patients consisted of 8 patients with simple steatosis (15%), 27 with borderline NASH (51%) and 18 with definitive NASH (34%). Metabolic syndrome was found in 62.2% of the patients with NAFLD. The mean serum LOX-1 level in biopsy-proven NAFLD patients was 8.49 ± 6.43 ng/mL compared to 4.08 ± 4.32 ng/mL in healthy controls (P = 0.001). The LOX-1 levels were significantly different between controls, simple steatosis and NASH (borderline+definite) cases (4.08 ± 4.32 ng/mL, 6.1 ± 6.16 ng/mL, 8.92 ± 6.45 ng/mL, respectively, P = 0.004). When the cut-off value for the serum LOX-1 level was set at 5.35 ng/mL, and a ROC curve analysis was performed to distinguish between steatohepatitis patients and controls; the sensitivity and specificity of the serum LOX-1 level were 69.8% and 69.2%, respectively. The serum LOX-1 levels were significantly higher in NAFLD patients than in healthy controls. Additionally, the serum LOX-1 levels could differentiate between steatohepatitis patients and healthy controls.

Serum lectin-like oxidized-low density lipoprotein receptor-1 and adiponectin levels are associated with coronary artery disease accompanied with metabolic syndrome.

Background:Coronary artery disease (CAD) is a major public health problem for developed and developing countries and is the single leading cause of death worldwide.Objectives:There is very few evidence regarding changes of both serum Lectin-like oxidized-low density lipoprotein receptor-1 (LOX-1) and adiponectin in patients with CAD accompanied with metabolic syndrome (MS). Here we aimed to evaluate serum levels of LOX-1 and adiponectin in patients with CAD accompanied with MS.Patients and Methods:Thirty patients with coronary artery disease without metabolic syndrome, 30 patients with coronary artery disease and metabolic syndrome, 30 ones with metabolic syndrome and 30 healthy subjects were enrolled. For all subjects, a questionnaire was filled to collect data, and peripheral blood samples were collected aseptically from the antecubital vein to measure serum Lectin-like oxidized-low density lipoprotein receptor-1 and adiponectin levels by enzyme-linked immunosorbent assay.Results:Serum LOX-1 level was highest in CAD + MS group; the difference between control and disease groups was statistically significant (P < 0.001). Adiponectin level had the lowest value in CAD + MS group; the difference between control and disease groups was statistically significant (P < 0.05). No significant differences were observed in serum Lectin-like oxidized-low density lipoprotein receptor-1and adiponectin in patients with different ages and gender. Serum LOX-1 level was changed negatively and linearly (R2 = 0.721) correlated with adiponectin level in different groups.Conclusions:Patient with CAD and MS had higher risk than those with only CAD because of lipid and glucose metabolism abnormalities. Combination measurements of serum LOX-1 and adiponectin levels may be helpful to evaluate the severity of CAD together with MS.

Significance of soluble lectin-like oxidized LDL receptor-1 levels in systemic and coronary circulation in acute coronary syndrome.

Background. Soluble lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) level is a novel biomarker for diagnosis of acute coronary syndrome (ACS); however, this level in the coronary circulation has yet to be examined. Methods. Twenty-seven consecutive patients with ACS and 40 patients with effort angina pectoris (EAP) undergoing percutaneous coronary intervention (PCI) had levels of soluble LOX-1 and LOX-1 index measured in paired blood samples from aorta (Ao) and coronary sinus (CS) just prior to the PCI. Results. We found positive correlations between soluble LOX-1 levels in the Ao and CS in both ACS and EAP patients (P < 0.01, for both). The soluble LOX-1 levels in the Ao and CS were higher in ACS than in EAP patients (P < 0.01, for both). The levels of soluble LOX-1 and LOX-1 index of the CS were significantly greater than those of the Ao in both ACS and EAP patients (P < 0.01, for both). Receiver operating characteristic curves for ACS detection demonstrated high sensitivity and specificity for the soluble LOX-1 and LOX-1 index with no differences between the Ao and CS. Conclusions. The present study showed that circulating soluble LOX-1 originates from coronary circulation and soluble LOX-1 and LOX-1 index are useful biomarkers for ACS.

Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Plays an Important Role in Vascular Inflammation in Current Smokers

Smoking induces vascular inflammation and increases the risk of cardiovascular events. Lectinlike oxidized low-density lipoprotein receptor-1 (LOX-1) is a scavenger receptor that is induced by oxidative stress and is associated with atherosclerotic plaque formation and destabilization. LOX-1 interacts with C-reactive protein (CRP) and plays an important role in inflammatory diseases. We therefore hypothesized that LOX-1 may be involved in the onset of smoking-induced vascular inflammation. We measured the soluble LOX-1 (sLOX-1) levels in sera obtained from 207 current smokers. The serum sLOX-1 levels positively correlated with various smoking variables, such as the number of cigarettes smoked per day (r= 0.150, p<0.05), the expired air carbon monoxide (CO) concentrations (r= 0.198, p<0.005) and the Fagerstrom test for nicotine dependence scores (r= 0.190, p<0.01). The serum levels of sLOX-1 also correlated with those of a representative inflammatory marker, the serum high-sensitivity CRP level (hsCRP; r= 0.232, p<0.005). A multivariate regression analysis revealed the independent determinants of the serum sLOX-1 level to be the expired air CO concentration (β= 0.182, p<0.05) and the hsCRP level (β= 0.213, p<0.01). The serum sLOX-1 level was found to increase in close association with both the smoking-related variables and the inflammatory marker hsCRP. These findings suggest that LOX-1 may therefore play an important role in the onset of smoking-induced inflammation and atherosclerosis in humans.

Circulating soluble lectin-like oxidized low-density lipoprotein receptor-1 levels are associated with proximal/middle segment of the LAD lesions in patients with stable coronary artery disease

Atherosclerosis is the main underlying pathology of coronary artery disease (CAD), which is the leading cause of mortality worldwide. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is involved in multiple phases of vascular dysfunction, including endothelial dysfunction, atherosclerotic plaque formation, and destabilization. The purpose of the current study was to determine whether soluble LOX-1 is associated with proximal/mid and distal segment of the left anterior descending (LAD) artery lesion in patients with stable CAD. Sixty-four patients with proximal/mid segment of the LAD lesions and 51 patients with distal segments of the LAD lesions were included in this study. Soluble LOX-1 levels were measured in all study subjects. Baseline characteristics of the two groups were similar. In stable CAD, patients with proximal/middle segment of the LAD lesions had significantly higher circulating soluble LOX-1 levels than patients with distal segments of the LAD lesions (1.07±0.33 vs. 0.70±0.17ng/ml, p<0.001). No correlation was found between plasma-soluble LOX-1 levels and fasting glucose, lipid profile. For predicting proximal/middle LAD lesions, the highest specificity (95,2%) and sensitivity (53,8%) levels were obtained at the cut-off value of 0.68. Our study demonstrated that serum-soluble LOX-1 levels were associated with proximal/mid segment of the LAD lesions. Furthermore, this study suggested soluble LOX-1 might be a useful biomarker of coronary plaque vulnerability in patients with stable CAD. Soluble LOX-1, the novel biochemical marker, may provide new insights into not only risk stratification but also therapeutic strategy for CAD.

CRP enhances soluble LOX-1 release from macrophages by activating TNF-α converting enzyme

Circulating levels of soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) play an important role in the development and progression of atherosclerosis. We hypothesized that the inflammatory marker C-reactive protein (CRP) might stimulate sLOX-1 release by activating tumor necrosis factor-α converting enzyme (TACE). Macrophages differentiated from THP-1 cells were stimulated with TNF-α and further treated with CRP in the absence or presence of specific inhibitors or small interfering RNA (siRNA). Our results showed that CRP increased sLOX-1 release from activated macrophages in a dose-dependent manner and that these effects were regulated by Fc γ receptor II (FcγRII)-mediated p47(phox) phosphorylation, reactive oxygen species (ROS) production, and TACE activation. CRP also enhanced sLOX-1 release from macrophages derived from peripheral blood mononuclear cells (PBMC) of patients with acute coronary syndrome (ACS). Pretreatment with antibody against FcγRII or with CD32 siRNA, p47(phox) siRNA, apocynin, N-acetylcysteine, tumor necrosis factor-α protease inhibitor 1 (TAPI-1) or TACE siRNA attenuated sLOX-1 release induced by CRP. CRP also elevated serum sLOX-1 levels in a rabbit model of atherosclerosis. Thus, CRP might stimulate sLOX-1 release, and the underlying mechanisms possibly involved FcγRII-mediated p47(phox) phosphorylation, ROS production, and TACE activation.

Restraint stress up-regulates lectin-like oxidized low-density lipoprotein receptor-1 in aorta of apolipoprotein E-deficient mice

Psychological stress is a risk factor for cardiovascular disease including atherosclerosis, but the mechanisms are unknown. The vascular lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is involved in vascular pathology and early atherogenesis. We hypothesized that LOX-1 is up-regulated by psychological stress via the formation of oxygen-derived free radicals, and that treatment with EUK-8 (a superoxide dismutase and catalase mimetic) prevents production of oxygen-derived free radicals and leads to reduced expression of LOX-1 in the vascular wall. As a model for psychological stress, we exposed male apolipoprotein E-deficient mice to repeated restraint stress by placement in a conical tube for 2 h per day for 14 consecutive days. Stressed and control mice were treated with EUK-8 (n = 4–5) or vehicle (n = 4–5). Reactive oxygen species and peroxynitrite levels, as detected by oxidative fluorescence microscopy, were increased in the aortic root of mice exposed to stress compared to those of controls by 212 ± 22% (mean ± SEM; p < 0.001) and 110 ± 6% (p < 0.001), respectively. LOX-1, as detected by immunohistochemistry, was increased by 443 ± 63% in stressed mice compared to control mice (p < 0.001). EUK-8 reduced reactive oxygen species, peroxynitrite, and LOX-1 levels in stressed mice compared to vehicle-treated stressed mice. To conclude, LOX-1 induced by reactive oxygen species and/or peroxynitrite could be one mechanism by which stress promotes cardiovascular disease.

Soluble lectin-like oxidized LDL receptor-1 (sLOX-1) as a sensitive and specific biomarker for acute coronary syndrome—Comparison with other biomarkers

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) appears to be involved in atherosclerotic plaque vulnerability and rupture. Circulating soluble LOX-1 (sLOX-1) levels are dramatically elevated in patients with acute coronary syndrome (ACS), and its diagnostic sensitivity and specificity is superior to high-sensitivity C-reactive protein (hs-CRP). In this study, we have compared the diagnostic value of sLOX-1 for ACS with those of troponin T (TnT) and heart-type fatty acid binding protein (H-FABP). One hundred and seven patients who underwent coronary angiography (CAG), including 18 ACS and 89 non-ACS patients were enrolled. Peripheral blood samples were obtained during the emergent or elective CAG. The non-ACS group consisted of 30 patients with normal CAG, 30 stable angina pectoris patients controlled by medical treatment, and 29 patients with stable angina who required elective coronary revascularization (percutaneous coronary intervention or coronary artery bypass graft). Age, gender, lipid profiles, or prevalence of diabetes, smoking, or hypertension were not significantly different between ACS and non-ACS. These factors did not significantly affect blood sLOX-1 levels. Circulating sLOX-1, TnT, and H-FABP levels were significantly higher in ACS than non-ACS. Area under the curve (AUC) values of the receiver-operating characteristic curves were 0.948, 0.704, and 0.691 for sLOX-1, TnT, and H-FABP, respectively. In a TnT-negative (<0.03 ng/mL) subgroup, the AUC values for sLOX-1 and H-FABP were 0.848 and 0.476, respectively. Circulating sLOX-1 is a more sensitive and specific biomarker for ACS than TnT and H-FABP, and provides additional diagnostic values when measured in combination with TnT.

Lectin-Like Oxidized Low Density Lipoprotein Receptor 1 (LOX-1) in Atherogenesis: A Brief Review

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a scavenger receptor that primarily binds and regulates oxidized low-density lipoprotein (LDL). Expression of LOX-1 is regulated by a feed-forward system stimulated by oxidized LDL (oxLDL), a major component of atherosclerosis. LOX-1 is a homodimer with a reactive backbone that can bind to a host of different ligands, including small molecules, and whole cells. LOX-1 is involved in many intercellular, intracellular, and molecular processes that are atherogenic. LOX-1 levels are elevated within atherosclerotic plaques and its expression is induced by proinflammatory cytokines. The ability of LOX-1 to bind many different ligands and control several atherogenic processes makes this receptor a likely vascular disease biomarker as well as an ideal choice for drug therapy aimed at preventing cardiovascular disease.

Circulating Levels of Lectin‐Like Oxidized Low‐Density Lipoprotein Receptor‐1 are Associated with Inflammatory Markers

Lectin-like oxidized-low-density lipoprotein receptor-1 (LOX-1) is increasingly linked to atherosclerotic plaque formation and the soluble form of this receptor may reflect activities of disease. We investigated the associations among levels of sLOX-1, oxidized-low-density lipoprotein (ox-LDL), cytokines and the extension of atherosclerosis in patients with coronary artery disease (CAD). Lipid, TNF-alpha, IL-6, C reactive protein (CRP), ox-LDL, peroxy radical and sLOX-1 levels were measured in 29 controls and 60 patients with CAD, 30 of which with one or two vessels involved (group 1), and 30 patients with three or four vessels involved (group 2). The serum levels of sLOX-1 were significantly and progressively higher in group 1 [611 (346-1,313) pg/ml, median (interquartile range)] and in group 2 [2,143 (824-3,201) pg/ml] than in control subjects [268 (111-767) pg/ml]. LOX-1 levels positively correlated with IL-6 (r = 0.38, P = 0.0042), TNF-alpha (r = 0.38, P = 0.0037), CRP levels (r = 0.32, P = 0.027) and age (r = 0.25, P = 0.048). In the multivariate analysis TNF-alpha resulted the only independent determinant of LOX-1 serum levels (beta-value = 0.304, P = 0.017). These findings suggest that sLOX-1 levels are up-regulated during CAD progression and are associated with inflammatory markers. The measurement of the circulating soluble form of this receptor may be potentially useful in predicting CAD progression in humans.