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

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 Significance of Soluble Lectin-Like Oxidized LDL Receptor-1 Levels in Systemic and Coronary Circulation in Acute Coronary Syndrome

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Tomofumi Misaka ◽  
Satoshi Suzuki ◽  
Nobuo Sakamoto ◽  
Takayoshi Yamaki ◽  
Koichi Sugimoto ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Coronary Circulation ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
High Sensitivity ◽  
Coronary Intervention ◽  
Coronary Syndrome ◽  
Density Lipoprotein Receptor

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.

scholarly journals Role of Lectin-Like Oxidized Low Density Lipoprotein-1 in Fetoplacental Vascular Dysfunction in Preeclampsia

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Felipe A. Zuniga ◽  
Valeska Ormazabal ◽  
Nicolas Gutierrez ◽  
Valeria Aguilera ◽  
Claudia Radojkovic ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Vascular Dysfunction ◽  
Pathological Condition ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Fetal Loss ◽  
Density Lipoprotein ◽  
Placental Tissue

The bioavailability of nitric oxide (NO) represents a key marker in vascular health. A decrease in NO induces a pathological condition denominated endothelial dysfunction, syndrome observed in different pathologies, such as obesity, diabetes, kidney disease, cardiovascular disease, and preeclampsia (PE). PE is one of the major risks for maternal death and fetal loss. Recent studies suggest that the placenta of pregnant women with PE express high levels of lectin-like oxidized LDL receptor-1 (LOX-1), which induces endothelial dysfunction by increasing reactive oxygen species (ROS) and decreasing intracellular NO. Besides LOX-1 activation induces changes in migration and apoptosis of syncytiotrophoblast cells. However, the role of this receptor in placental tissue is still unknown. In this review we will describes the physiological roles of LOX-1 in normal placenta development and the potential involvement of this receptor in the pathophysiology of PE.

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.

scholarly journals Soluble Lectin-Like Oxidized Low Density Lipoprotein Receptor-1 as a Biochemical Marker for Atherosclerosis-Related Diseases

2013 ◽  
Vol 35 ◽  
pp. 413-418 ◽  
Author(s):  
Angela Pirillo ◽  
Alberico Luigi Catapano
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Coronary Intervention ◽  
Soluble Form ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Oxidized Low Density Lipoprotein ◽  
Low Density Lipoprotein Receptor ◽  
Coronary Syndrome ◽  
Density Lipoprotein Receptor

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.

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.

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