The G501C Polymorphism of the Oxidized Low-Density Lipoprotein-Receptor 1 Gene Is Associated with Acute Coronary Syndrome in the Han Chinese Population

Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1), the main oxidized low-density lipoprotein (OxLDL) in endothelial cells, is upregulated in atherosclerotic lesions and is involved in several cellular processes that regulate the pathogenesis of atherosclerosis. The LOX-1 expressed on the cell surface can be proteolytically cleaved and released in a soluble form (sLOX-1) in the circulation under pathological conditions. Serum levels of sLOX-1, in fact, are elevated at the early stages of acute coronary syndrome and are associated with coronary plaque vulnerability and with the presence of multiple complex coronary lesions. Moreover, in subjects with stable CAD, levels of serum sLOX-1 are associated with the presence of lesions in the proximal and mid-segments of the left anterior descending artery that are the most prone to rupture; in subjects undergoing percutaneous coronary intervention, baseline preprocedural serum sLOX-1 levels are associated with the incidence of periprocedural myocardial infarction. Altogether, these findings suggest that circulating levels of sLOX-1 might be a diagnostic and prognostic marker for atherosclerotic-related events.

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Abstract 559: Lectin-like Oxidised Low Density Lipoprotein Receptor-1 Expression in Atheroma of Patients with Coronary Artery Disease is Higher in Patients with Acute Coronary Syndrome but Decreased in Patients on Statins

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.36.suppl_1.559 ◽

2016 ◽

Vol 36 (suppl_1) ◽

Author(s):

Martin Landsberger ◽

Jens Ackermann ◽

Stephan B Felix ◽

Johannes B Dahm

Keyword(s):

Body Mass Index ◽

Acute Coronary Syndrome ◽

Atherosclerotic Plaque ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Low Density ◽

Lipoprotein Receptor ◽

Coronary Syndrome ◽

Density Lipoprotein Receptor ◽

Oxidised Low Density Lipoprotein

Introduction: The lectin-like oxidised low density lipoprotein receptor-1, LOX-1, is expressed in endothelial cells and macrophages among others. Its expression can be induced by a variety of stimuli such as oxidised LDL, endothelin-1, angiotensin II and shear stress. LOX-1 seems to be important for the induction of endothelial dysfunction and is implicated in atherosclerotic plaque vulnerability. Methods: Atherectomy specimens were obtained from 37 patients (mean age 62.5±9.7 years, body mass index 28.6±5.3 kg/m2; n=30 with chest pain/angina pectoris), who underwent medially indicated directional coronary atherectomy in the Department of Internal Medicine B, University Medicine Greifswald, between July 2001 and April 2005, and were immediately frozen in liquid nitrogen. Human coronary atherectomy specimens were cut into 5 μm-slices using a kryotom and stained with haematoxylin and eosin (H&E), Oil Red O (lipids) and Elastica-van Gieson (collagen). LOX-1 was detected by immunofluorescence using a FITC-labelled rabbit polyclonal antibody against amino acids 143 to 271 of human LOX-1. Digital images were analysed with Corel PHOTO-PAINT 12, SCION Image, and SigmaPlot 11. Correlations between signal intensities for LOX-1 expression and patients’ parameters were analysed by Spearman Rank Order testing. Patients gave informed consent. The study protocol complied with the Declaration of Helsinki and was approved by the local ethics committee. Results: LOX-1 expression correlated significantly with lipid content of the coronary atherectomy specimens. LOX-1 expression tended to be higher in specimens from patients with acute coronary syndrome (n=11) and to be lower in patients receiving statins (n=16). However, no correlations were found between LOX-1 expression and grade of stenosis, plaque localisation, age, sex, body mass index, smoking (n=15), hypertension (n=31), diabetes mellitus type II (n=9), and dyslipoproteinaemia (n=32). Conclusions: LOX-1 expression in plaques was positively correlated with lipid contents of plaque material and tended to be higher in patients with acute coronary syndrome and to be lower if patients had received statins. High LOX-1 expression in the atherosclerotic plaque may contribute to plaque instability.

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The Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 and its Soluble Form: Cardiovascular Implications

Journal of Atherosclerosis and Thrombosis ◽

10.5551/jat.3228 ◽

2010 ◽

Vol 17 (4) ◽

pp. 317-331 ◽

Cited By ~ 50

Author(s):

Teresa Navarra ◽

Serena Del Turco ◽

Sergio Berti ◽

Giuseppina Basta

Keyword(s):

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Soluble Form ◽

Low Density ◽

Lipoprotein Receptor ◽

Oxidized Low Density Lipoprotein ◽

Low Density Lipoprotein Receptor ◽

Density Lipoprotein Receptor

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

Clinical Science ◽

10.1042/cs20180639 ◽

2018 ◽

Vol 132 (21) ◽

pp. 2369-2381 ◽

Cited By ~ 5

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.

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