scholarly journals Structure and chromosomal assignment of the human lectin-like oxidized low-density-lipoprotein receptor-1 (LOX-1) gene

1999 ◽  
Vol 339 (1) ◽  
pp. 177-184 ◽  
Author(s):  
Takuma AOYAMA ◽  
Tatsuya SAWAMURA ◽  
Yoshiyuki FURUTANI ◽  
Rumiko MATSUOKA ◽  
Michihiro C. YOSHIDA ◽  
...  
Keyword(s):  
Transcription Initiation ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Regulatory Region ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Regulatory Elements ◽  
Initiation Site ◽  
Chromosomal Assignment ◽  
Low Density

We have reported the cDNA cloning of a modified low-density-lipoprotein (LDL) receptor, designated lectin-like oxidized LDL receptor-1 (LOX-1), which is postulated to be involved in endothelial dysfunction and the pathogenesis of atherosclerosis. Here, we determined the organization of the human LOX-1 gene, including the 5´-regulatory region. The 5´-regulatory region contained several potential cis-regulatory elements, such as GATA-2 binding element, c-ets-1 binding element, 12-O-tetradecanoylphorbol 13-acetate-responsive element and shear-stress-responsive elements, which may mediate the endothelium-specific and inducible expression of LOX-1. The major transcription-initiation site was found to be located 29 nucleotides downstream of the TATA box and 61 nucleotides upstream from the translation-initiation codon. The minor initiation site was found to be 5 bp downstream from the major site. Most of the promoter activity of the LOX-1 gene was ascribed to the region (-150 to -90) containing the GC and CAAT boxes. The coding sequence was divided into 6 exons by 5 introns. The first 3 exons corresponded to the different functional domains of the protein (cytoplasmic, transmembrane and neck domains), and the residual 3 exons encoded the carbohydrate-recognition domain similar to the case of other C-type lectin genes. The LOX-1 gene was a single-copy gene and assigned to the p12.3–p13.2 region of chromosome 12. Since the locus for a familial hypertension has been mapped to the overlapping region, LOX-1 might be the gene responsible for the hypertension.

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1): a crucial driver of atherosclerotic cardiovascular disease

2020 ◽  
Author(s):  
Alexander Akhmedov ◽  
Tatsuya Sawamura ◽  
Chu-Huang Chen ◽  
Simon Kraler ◽  
Daria Vdovenko ◽  
...  
Keyword(s):  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Basic Research ◽  
Plaque Formation ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Atheromatous Plaques

Abstract Cardiovascular diseases (CVDs), specifically lipid-driven atherosclerotic CVDs, remain the number one cause of death worldwide. The lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1), a scavenger receptor that promotes endothelial dysfunction by inducing pro-atherogenic signalling and plaque formation via the endothelial uptake of oxidized LDL (oxLDL) and electronegative LDL, contributes to the initiation, progression, and destabilization of atheromatous plaques, eventually leading to the development of myocardial infarction and certain forms of stroke. In addition to its expression in endothelial cells, LOX-1 is expressed in macrophages, cardiomyocytes, fibroblasts, dendritic cells, lymphocytes, and neutrophils, further implicating this receptor in multiple aspects of atherosclerotic plaque formation. LOX-1 holds promise as a novel diagnostic and therapeutic target for certain CVDs; therefore, understanding the molecular structure and function of LOX-1 is of critical importance. In this review, we highlight the latest scientific findings related to LOX-1, its ligands, and their roles in the broad spectrum of CVDs. We describe recent findings from basic research, delineate their translational value, and discuss the potential of LOX-1 as a novel target for the prevention, diagnosis, and treatment of related CVDs.

scholarly journals The Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 and Cardiovascular Disease

1970 ◽  
Vol 3 (2) ◽  
pp. 169-177
Author(s):  
MSA Sheikh ◽  
T Yang ◽  
U Salma ◽  
M Ali
Keyword(s):  
Signal Transduction ◽  
Endothelial Dysfunction ◽  
Morphological Changes ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Soluble Form ◽  
Low Density ◽  
Coronary Syndrome

Lectin-like oxidized LDL receptor-1 (LOX-1), a lectin-like 50-kD receptor for oxidized low-density lipoproteins (ox-LDL), is present primarily on endothelial cells. Oxidatively modified low-density lipoprotein (oxLDL) is implicated in the pathogenesis of atherosclerosis. Endothelial dysfunction is the initial change in the vascular wall that induces morphological changes for atheroma-formation. LOX-1 was identified as the receptor for oxLDL that was thought to be a major cause of endothelial dysfunction. LOX-1 has been demonstrated to contribute not only to endothelial dysfunction, but also to atherosclerotic-plaque formation, hypertension, myocardial infarction and intimal thickening after balloon injury. Studies with transgenic and knockout mouse models have elucidated in part the role of LOX-1 in the pathogenesis of atherosclerosis and cardiac remodeling. Recently, a circulating soluble form of LOX-1(sLOx-1), corresponding solely to its extracellular domain, has been identified in human serum. Circulating levels of sLOX-1 are increased in inflammatory and atherosclerotic conditions and are associated with acute coronary syndrome, with the severity of coronary artery disease, and with serum biomarkers for oxidative stress and inflammation, suggesting that they could be useful marker for vascular injury. Identification and regulation of this receptor and understanding of signal transduction pathways might open new gateways from diagnosis to therapeutics for cardiovascular diseases. Keywords: Atherosclerosis; Endothelial dysfunction; LOX-1; ox-LDL; Signal transduction. DOI: http://dx.doi.org/10.3329/cardio.v3i2.9187 Cardiovasc. J. 2011; 3(2): 169-177

scholarly journals Chemical composition-oriented receptor selectivity of L5, a naturally occurring atherogenic low-density lipoprotein

2011 ◽  
Vol 83 (9) ◽  
pp. 1731-1740 ◽  
Author(s):  
Liang-Yin Ke ◽  
David A. Engler ◽  
Jonathan Lu ◽  
Risë K. Matsunami ◽  
Hua-Chen Chan ◽  
...  
Keyword(s):  
Chemical Composition ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Low Density ◽  
Protein Distribution ◽  
Receptor Selectivity

Anion-exchange chromatography resolves human plasma low-density lipoprotein (LDL) into 5 subfractions, with increasing negative surface charge in the direction of L1 to L5. Unlike the harmless L1 to L4, the exclusively atherogenic L5 is rejected by the normal LDL receptor (LDLR) but endocytosed into vascular endothelial cells (ECs) through the lectin-like oxidized LDL receptor-1 (LOX-1). Analysis with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and 2-dimensional electrophoresis showed that the protein framework of L1 was composed mainly of apolipoprotein (apo) B100, with an isoelectric point (pI) of 6.620. There was a progressively increased association of additional proteins, including apoE (pI 5.5), apoAI (pI 5.4), apoCIII (pI 5.1), and apo(a) (pI 5.5), from L1 to L5. Liquid chromatography data-independent parallel-fragmentation mass spectrometry (LC/MSE) was used to quantify protein distribution in all subfractions. On the basis of weight percentages, L1 contained 99 % apoB-100 and trace amounts of other proteins. In contrast, L5 contained 60 % apoB100 and substantially increased amounts of apo(a), apoE, apoAI, and apoCIII. The compositional characteristics contribute to L5’s electronegativity, rendering it unrecognizable by LDLR. LOX-1, which has a high affinity for negatively charged ligands, is known to mediate the signaling of proinflammatory cytokines. Thus, the chemical composition-oriented receptor selectivity hinders normal metabolism of L5, enhancing its atherogenicity through abnormal receptors, such as LOX-1.

scholarly journals “Benifuuki” Extract Reduces Serum Levels of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Ligands Containing Apolipoprotein B: A Double-Blind Placebo-Controlled Randomized Trial

Nutrients ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 924
Author(s):  
Masahiro Miyawaki ◽  
Hiroyuki Sano ◽  
Hisashi Imbe ◽  
Reiko Fujisawa ◽  
Keiji Tanimoto ◽  
...  
Keyword(s):  
Ldl Cholesterol ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Ice Cream ◽  
Serum Levels ◽  
High Dose ◽  
Low Density ◽  
Double Blind

(1) Background: Arteriosclerosis is associated with high levels of low-density lipoprotein (LDL) cholesterol. O-methylated catechins in “Benifuuki” green tea are expected to reduce cholesterol levels, although there is limited research regarding this topic; (2) Methods: This trial evaluated 159 healthy volunteers who were randomized to receive ice cream containing a high-dose of “Benifuuki” extract including 676 mg of catechins (group H), a low-dose of “Benifuuki” extract including 322 mg of catechins (group L), or no “Benifuuki” extract (group C). Each group consumed ice cream (with or without extract) daily for 12 weeks, and their lipid-related parameters were compared; (3) Results: A significant reduction in the level of lectin-like oxidized LDL receptor-1 ligand containing ApoB (LAB) was detected in group H, compared to groups L and C. No significant differences between the three groups were detected in their levels of total cholesterol, triglycerides, and LDL cholesterol; (4) Conclusions: “Benifuuki” extract containing O-methylated catechins may help prevent arteriosclerosis.

scholarly journals Association between Negatively Charged Low-Density Lipoprotein L5 and Subclinical Atherosclerosis in Rheumatoid Arthritis Patients

2019 ◽  
Vol 8 (2) ◽  
pp. 177 ◽  
Author(s):  
Chun-Yu Chang ◽  
Chu-Huang Chen ◽  
Yi-Ming Chen ◽  
Tsu-Yi Hsieh ◽  
Ju-Pi Li ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Oxidized Ldl ◽  
Subclinical Atherosclerosis ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Intima Media Thickness ◽  
Low Density ◽  
Receiver Operating Characteristic Curves ◽  
The Relationship

L5, the most negatively charged subfraction of low-density lipoprotein (LDL), is implicated in atherogenesis. We examined the relationship between plasma L5 levels and the occurrence of subclinical atherosclerosis in patients with rheumatoid arthritis (RA). Using anion-exchange purification with fast-protein liquid chromatography, we determined the proportion of plasma L5 of LDL (L5%) in 64 RA patients and 12 healthy controls (HC). Plasma L5% and L5 levels were significantly higher in RA patients (median, 1.4% and 1.92 mg/dL) compared with HC (0.9%, p < 0.005; and 1.27 mg/dL, p < 0.05) and further increased in patients with subclinical atherosclerosis (2.0% and 2.88 mg/dL). L5% and L5 levels decreased in patients after 6-months of therapy (p < 0.01). Subclinical atherosclerosis was indicated by plaque and intima-media thickness determined by carotid ultrasonography. Using multivariate analysis, L5% and L5 levels are revealed as the predictors of subclinical atherosclerosis (odds ratio, 4.94 and 1.01; both p < 0.05). Receiver operating characteristic curves showed that cut-off values of L5% ≥ 1.45% and L5 levels ≥ 2.58 mg/dL could predict subclinical atherosclerosis in patients (both p < 0.001). Immunoblotting showed that the expression levels of lectin-like oxidized LDL receptor-1 (LOX-1) was increased in RA patients. Together, our findings suggest that plasma L5% and L5 levels may be predictors of cardiovascular risk in RA patients.

scholarly journals Identification of the lectin-like receptor for oxidized low-density lipoprotein in human macrophages and its potential role as a scavenger receptor

1998 ◽  
Vol 334 (1) ◽  
pp. 9-13 ◽  
Author(s):  
Hiroshi YOSHIDA ◽  
Nonna KONDRATENKO ◽  
Simone GREEN ◽  
Daniel STEINBERG ◽  
Oswald QUEHENBERGER
Keyword(s):  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Scavenger Receptor ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Human Monocyte ◽  
Binding Activity ◽  
Low Density ◽  
Blood Monocytes ◽  
Oxidized Low Density Lipoprotein

A new receptor for oxidized low-density lipoprotein (LDL), lectin-like oxidized LDL receptor-1 (LOX-1), has recently been cloned from bovine endothelial cells and human lung. A limited tissue-distribution study suggested that the protein was mainly produced by the vascular endothelium. In the present study we demonstrate that LOX-1 is also expressed in macrophages, where it may function as a scavenger receptor. LOX-1 was not detected in undifferentiated THP-1 cells or in freshly isolated human blood monocytes. However, mature human monocyte-derived macrophages and differentiated THP-1 cells showed high levels of LOX-1 transcripts. Consistent with these results, immunofluorescence staining and FACS analysis demonstrated that LOX-1 protein is expressed on the plasma membrane of macrophages. Western-blot analysis of membranes from macrophages (but not those from monocytes) identified a single band, with an apparent molecular mass of about 40 kDa, that displayed oxidized LDL-binding activity. These results suggest that differentiation induces the expression of LOX-1 in macrophages, where it may play a role as a scavenger receptor and/or a receptor for oxidized LDL.

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