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

Abstract

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.

Interleukin-1β Promotes Ox-LDL Uptake by Human Glomerular Mesangial Cells via LOX-1

“…Recently, LOX-1 is being viewed as a critical mediator of atherosclerosis and vascular inflammation. Elevated serum levels of soluble LOX-1, a fragment of the main LOX-1 molecule, have been evaluated as promising biomarkers for diagnosis and risk assessment of metabolic syndrome and coronary artery disease among the metabolic syndrome population [7].The present study on arthritis has demonstrated the roles…”

Association of circulating soluble lectin-like oxidized low-density lipoprotein receptor-1 with inflammatory markers and urinary albumin excretion in patients with type 2 diabetes

“…However, we could not confirm a potential elevation of sLOX-1 in our patients because we did not measure sLOX-1 levels in healthy control subjects. Notably, recent studies have shown significantly higher circulating sLOX-1 levels in patients with single-, double-, and multiple-vessel coronary artery disease (CAD) 43 or in those with CAD complicated by metabolic syndrome, 44 compared to healthy subjects. In addition, baseline sLOX-1 concentrations have been found to be correlated with major adverse cardiovascular events (MACE) in patients with stable CAD, 45 and there may be a further increase of sLOX-1 in situations of ulcerated plaques.…”

A novel insight into the nature of modified low-density lipoproteins and their role in atherosclerosis

“…This finding was confirmed in a study using oral administration of urea to Apoe -/mice leading to an eight-fold increase in blood cLDL levels and more severe progression of atherosclerosis than in control mice [190] . Due to myeloperoxidase, there is an alternative mechanism in which thiocyanate is oxidized in the presence of H 2 O 2 to cyanate in smokers [191,192] .…”