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http://purl.uniprot.org/citations/28199510http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/28199510http://www.w3.org/2000/01/rdf-schema#comment"

Aims

The lectin-like oxLDL receptor-1 (LOX-1) promotes endothelial uptake of oxidized low-density lipoprotein (oxLDL) and plays an important role in atherosclerosis and acute coronary syndromes (ACS). However, its role in arterial thrombus formation remains unknown. We investigated whether LOX-1 plays a role in arterial thrombus formation in vivo at different levels of oxLDL using endothelial-specific LOX-1 transgenic mice (LOX-1TG) and a photochemical injury thrombosis model of the carotid artery.

Methods and results

In mice fed a normal chow diet, time to arterial occlusion was unexpectedly prolonged in LOX-1TG as compared to WT. In line with this, tissue factor (TF) expression and activity in carotid arteries of LOX-1TG mice were reduced by half. This effect was mediated by activation of octamer transcription factor 1 (Oct-1) leading to upregulation of the mammalian deacetylase silent information regulator-two 1 (SIRT1) via binding to its promoter and subsequent inhibition of NF-κB signaling. In contrast, intravenous injection of oxLDL as well as high cholesterol diet for 6 weeks led to a switch from the Oct-1/SIRT1 signal transduction pathway to the ERK1/2 pathway and in turn to an enhanced thrombotic response with shortened occlusion time.

Conclusions

Thus, LOX-1 differentially regulates thrombus formation in vivo depending on the degree of activation by oxLDL. At low oxLDL levels LOX-1 activates the protective Oct-1/SIRT1 pathway, while at higher levels of the lipoprotein switches to the thrombogenic ERK1/2 pathway. These findings may be important for arterial thrombus formation in ACS and suggest that SIRT1 may represent a novel therapeutic target in this context."xsd:string
http://purl.uniprot.org/citations/28199510http://purl.org/dc/terms/identifier"doi:10.1093/cvr/cvx015"xsd:string
http://purl.uniprot.org/citations/28199510http://purl.uniprot.org/core/author"Costantino S."xsd:string
http://purl.uniprot.org/citations/28199510http://purl.uniprot.org/core/author"Manz J."xsd:string
http://purl.uniprot.org/citations/28199510http://purl.uniprot.org/core/author"Breitenstein A."xsd:string
http://purl.uniprot.org/citations/28199510http://purl.uniprot.org/core/author"Stivala S."xsd:string
http://purl.uniprot.org/citations/28199510http://purl.uniprot.org/core/author"Luscher T.F."xsd:string
http://purl.uniprot.org/citations/28199510http://purl.uniprot.org/core/author"Beer J.H."xsd:string
http://purl.uniprot.org/citations/28199510http://purl.uniprot.org/core/author"Akhmedov A."xsd:string
http://purl.uniprot.org/citations/28199510http://purl.uniprot.org/core/author"Lohmann C."xsd:string
http://purl.uniprot.org/citations/28199510http://purl.uniprot.org/core/author"Camici G.G."xsd:string
http://purl.uniprot.org/citations/28199510http://purl.uniprot.org/core/author"Holy E.W."xsd:string
http://purl.uniprot.org/citations/28199510http://purl.uniprot.org/core/author"Spescha R.D."xsd:string
http://purl.uniprot.org/citations/28199510http://purl.uniprot.org/core/author"Speer T."xsd:string
http://purl.uniprot.org/citations/28199510http://purl.uniprot.org/core/author"Paneni F."xsd:string
http://purl.uniprot.org/citations/28199510http://purl.uniprot.org/core/author"Reiner M.F."xsd:string
http://purl.uniprot.org/citations/28199510http://purl.uniprot.org/core/author"Schaub Clerigue A."xsd:string
http://purl.uniprot.org/citations/28199510http://purl.uniprot.org/core/author"Bonetti N.R."xsd:string
http://purl.uniprot.org/citations/28199510http://purl.uniprot.org/core/date"2017"xsd:gYear
http://purl.uniprot.org/citations/28199510http://purl.uniprot.org/core/name"Cardiovasc Res"xsd:string
http://purl.uniprot.org/citations/28199510http://purl.uniprot.org/core/pages"498-507"xsd:string
http://purl.uniprot.org/citations/28199510http://purl.uniprot.org/core/title"Endothelial LOX-1 activation differentially regulates arterial thrombus formation depending on oxLDL levels: role of the Oct-1/SIRT1 and ERK1/2 pathways."xsd:string
http://purl.uniprot.org/citations/28199510http://purl.uniprot.org/core/volume"113"xsd:string
http://purl.uniprot.org/citations/28199510http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/28199510
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