Abstract 12822: Increased Expression and Serum Levels of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 in Patients With Aortic Valve Stenosis

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Tomotaka Yoshiyama ◽  
Kei Yunoki ◽  
Ryushi Komatsu ◽  
Kazuo Haze ◽  
Takahiko Naruko ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Stenosis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Oxidized Low Density Lipoprotein ◽  
Control Subjects ◽  
Density Lipoprotein Receptor

Background: The development of aortic valve stenosis (AS) involves multiple events, including inflammation and lipid deposition and oxidation. 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. The aims of this study were to investigate the serum levels of sLOX-1 in patients with AS and also examine the expression of LOX-1 immunohistochemically in aortic valve specimens from these patients. Methods: Serum sLOX-1 levels were measured in patients with AS (n=128), stable angina pectoris (SAP, n=343) and in 53 control subjects using a sandwich ELISA method. Frozen aortic valve samples were also obtained surgically from a cohort of 20 AS patients. In addition, frozen aortic valve specimens were obtained at autopsy from individuals who died of non-cardiovascular causes (n = 11, mean age 68 yr) as a reference. Immunostaining of the samples was performed using antibodies against smooth muscle cells, macrophages, T-lymphocytes, neutrophils, microvessels, and LOX-1. Results: Serum sLOX-1 levels were significantly higher in AS patients compared with SAP patients ( P <0.0005) or control subjects ( P <0.0001). There were no differences in serum sLOX-1 levels between AS patients with or without coronary artery disease. Immunohistochemical staining showed that the LOX-1-positive area, as a percentage of the total area, was significantly (P<0.01) higher in AS patients compared with reference cases. Double immunostaining for LOX-1 and macrophages revealed that the vast majority of LOX-1-positive cells were macrophages. Conclusions: This study demonstrates for the first time that serum sLOX-1 levels are elevated in patients with AS, and AS lesions contain a significantly higher percentage of LOX-1-positive macrophages. These findings suggest that LOX-1, a marker of oxidative stress, may play an important role in the development of aortic valve stenosis.

scholarly journals 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

Medicina ◽  
2019 ◽  
Vol 55 (8) ◽  
pp. 493 ◽  
Author(s):  
Stankova ◽  
Delcheva ◽  
Maneva ◽  
Vladeva
Keyword(s):  
Coronary Artery Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Healthy Controls ◽  
Oxidized Low Density Lipoprotein ◽  
Density Lipoprotein Receptor ◽  
Artery Disease

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.

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

Folia Medica ◽  
2019 ◽  
Vol 61 (3) ◽  
pp. 419-425 ◽  
Author(s):  
Teodora R. Stankova ◽  
Ginka T. Delcheva ◽  
Ana I. Maneva ◽  
Stefka V. Vladeva
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Oxidized Low Density Lipoprotein ◽  
Density Lipoprotein Receptor

Introduction: 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. Aim: 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. Materials and methods: 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.Results: 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. Conclusions: The present study highlights the potential of cLDL, NT and sLOX-1 as possible markers of diabetic complications.

Alterations in vascular function by syncytiotrophoblast extracellular vesicles via lectin-like oxidized low-density lipoprotein receptor-1 in mouse uterine arteries

2018 ◽  
Vol 132 (21) ◽  
pp. 2369-2381 ◽  
Author(s):  
Floor Spaans ◽  
Anita Quon ◽  
Stewart R. Rowe ◽  
Jude S. Morton ◽  
Raven Kirschenman ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Extracellular Vesicles ◽  
Vascular Function ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Oxidized Low Density Lipoprotein ◽  
Uterine Arteries ◽  
Density Lipoprotein Receptor

Syncytiotrophoblast extracellular vesicles (STBEVs), released into the maternal circulation during pregnancy, have been shown to affect vascular function; however, the mechanism remains unknown. In rats, STBEVs were shown to reduce endothelium-mediated vasodilation via lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), a multi-ligand scavenger receptor that has been associated with vascular dysfunction. Recently, LOX-1 was shown to interact with the angiotensin II type 1 receptor (AT-1). We hypothesized that, in pregnant mice, STBEVs would impair vascular function via LOX-1 and would specifically affect angiotensin II responses. Uterine arteries from pregnant control (C57BL/6) and LOX-1 knockout (LOX-1KO) mice were isolated on gestational day (GD) 18.5. Endothelium-dependent (methylcholine (MCh); ± N(G)-Nitro-L-arginine methyl ester to assess nitric oxide (NO) contribution), and -independent (sodium nitroprusside) vasodilation, and vasoconstriction (angiotensin II; ± AT-1 [candesartan] or angiotensin II type 2 receptor (AT-2) [PD123.319] receptor antagonists; high potassium salt solution) responses were assessed using wire myography. AT-1 and AT-2 expression was analyzed using fluorescence microscopy. Human umbilical vein endothelial cells (HUVECs) were stimulated with STBEVs ± LOX-1 blocking antibody, and superoxide and peroxynitrite production were analyzed. Although MCh-induced vasodilation was decreased (P=0.0012), NO contribution to vasodilation was greater in LOX-1KO mice (P=0.0055). STBEVs delayed angiotensin II tachyphylaxis in arteries from control but not LOX-1KO mice (P<0.0001), while AT-1 and AT-2 expression was unchanged. STBEVs increased peroxynitrite production in HUVECs via LOX-1 (P=0.0091). In summary, LOX-1 deletion altered endothelium-mediated vasodilation, suggesting that LOX-1 contributes to vascular adaptations in pregnancy. STBEVs increased angiotensin II responsiveness and oxidative stress levels via LOX-1, suggesting that increased LOX-1 expression/activation or STBEVs could adversely affect vascular function and contribute to vascular complications of pregnancy.

Sign in / Sign up

Export Citation Format

Share Document