LOX-1 in atherosclerosis: biological functions and pharmacological modifiers

Xu, Suowen; Ogura, Sayoko; Chen, Jiawei; Little, Peter J.; Moss, Joel; Liu, Peiqing

doi:10.1007/s00018-012-1194-z

Cited by 250 publications

(227 citation statements)

References 112 publications

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“…LOX1 not only internalises modified lipids but also causes endothelial dysfunction, apoptosis, inflammation and smooth muscle cell proliferation, contributing to the process of atheroma formation at multiple levels (Xu et al 2013). LOX1 has been identified as the main endothelial receptor for oxLDL (Sawamura et al 1997).…”

Section: Discussionmentioning

confidence: 99%

oxLDL induces injury and defenestration of human liver sinusoidal endothelial cells via LOX1

Zhang¹,

Liu²,

Liu³

et al. 2014

Journal of Molecular Endocrinology

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Non-alcoholic fatty liver disease is associated with hepatic microangiopathy and liver inflammation caused by type 2 diabetes mellitus. Oxidised LDL (oxLDL) is involved in proinflammatory and cytotoxic events in various microcirculatory systems. The lectin-like oxLDL receptor 1 (LOX1) plays a crucial role in oxLDL-induced pathological transformation. However, the underlying mechanism of oxLDL's effects on liver microcirculation disturbances remains unclear. In this study, we investigated the effects of oxLDL on LOX1 (OLR1) expression and function, as well as on the fenestration features of human liver sinusoidal endothelial cells (HLSECs) in vitro. Primary HLSECs were obtained and cultured. The cells were treated with various concentrations of oxLDL (25, 50, 100 and 200 mg/ml), and the cytotoxicity and expression of LOX1 were examined. Furthermore, LOX1 knockdown was performed using siRNA technology, and the changes in intracellular reactive oxygen species (ROS), NFkB, p65, (p65), endothelin 1 (ET1 (EDN1)), eNOS (NOS3) and caveolin 1 (CAV1) levels were measured. Cells were treated with 100 mg/ml oxLDL, and the fenestra morphology was visualised using scanning electron microscopy. oxLDL significantly increased LOX1 expression at both the mRNA and protein levels in HLSECs in a dose-and time-dependent manner. oxLDL stimulation increased ROS generation and NFkB activation, upregulated ET1 and caveolin 1 expression, downregulated eNOS expression and reduced the fenestra diameter and porosity. All of these oxLDLmediated effects were inhibited after LOX1 knockdown. These results reveal a mechanism by which oxLDL stimulates the production of LOX1 through the ROS/NFkB signalling pathway and by which LOX1 mediates oxLDL-induced endothelial injury and the defenestration of HLSECs. Key Words" oxidised LDL " lectin-like oxLDL receptor 1 " endothelial injury " defenestration " human liver sinusoidal endothelial cells

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Section: Discussionmentioning

confidence: 99%

oxLDL induces injury and defenestration of human liver sinusoidal endothelial cells via LOX1

Zhang¹,

Liu²,

Liu³

et al. 2014

Journal of Molecular Endocrinology

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“…In addition to ox-LDL, these ligands include activated platelets, apoptotic bodies, bacteria, advanced glycation end products (AGEs), heat shock proteins (HSP60 and HSP70) and C-reactive protein (CRP) [62,68,70]. Beside endothelial cells, LOX-1 is expressed in several cell types including smooth muscle cells, fibroblasts and platelets [16,46,69].…”

Section: S Raniolo Et Al / Cholesterol Level Regulates Lectin-likementioning

confidence: 99%

“…Under physiological conditions, basal cellular LOX-1 expression is low in most tissues, while it is up-regulated in several pathophysiological processes such as inflammation, atherosclerosis, obesity and diabetes [59,68]. In this context, LOX-1 and ox-LDL contribute to plaque rupture in atherosclerosis by promoting lipid accumulation, oxidative stress, pro-inflammatory response, release of metalloproteinases and apoptotic cell death.…”

Section: Introductionmentioning

confidence: 99%

Cholesterol level regulates lectin-like oxidized low-density lipoprotein receptor-1 function

Raniolo

Vindigni

Biocca

2016

BSI

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Abstract. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), the primary receptor for ox-LDL in endothelial cells, is a multi-ligand scavenger receptor that plays a crucial role in the pathogenesis of atherosclerosis and cardiovascular disorders and recently identified as a tumor marker. LOX-1 is naturally present in caveolae/lipid rafts in plasma membranes and disruption of these membrane domains by cholesterol-lowering drugs leads to a spatial disorganization of LOX-1 and a marked loss of specific LOX-1 function in terms of ox-LDL binding and internalization. Moreover, cholesterol depletion triggers the release of LOX-1 in exosomes and enhances shedding of LOX-1 ectodomain.We here provide an overview of the involvement of membrane and circulating cholesterol in LOX-1 function and shedding and its impact on cardiovascular pathologies and cancer. In particular, we consider the available biological and molecular evidence indicating LOX-1 as a potential therapeutic target for atherosclerosis, inflammation processes, myocardial infarction and cholesterol-lowering drugs as specific inhibitors of LOX-1 function.

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“…The chemical structure of TSN and CPT are illustrated in Figure 1. Over the past decade, we [1,[10][11][12][13][14][15][16][17][18][19] and others [20][21][22][23][24] have demonstrated that TSN has potential protective effects against atherosclerosis, cardiac hypertrophy, cardiac fibrosis, diabetes, neurodegenerative diseases, and various kinds of cancers. However, the poor water-solubility, poor intestinal absorption, and low oral bioavailability (about 2.9 --3.4% in rats) [25] have hampered the clinical application of TSN.…”

Section: Tanshinone Ii-amentioning

confidence: 99%