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P46 Oxidisedoxidized LDL and LOX-1 scavenger receptor regulation of pro-atherogenic signal transduction
  1. I Abdul Zani1,
  2. N Mughal2,
  3. S Wheatcroft2,
  4. S Ponnambalam1
  1. 1School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, UK
  2. 2Faculty of Medicine and Health, University of Leeds, UK


Atherosclerosis is a chronic inflammatory disease characterised by lipid-laden lesions within arterial blood vessel walls. Inflammation is a central driver in atherosclerosis and is regulated by different signal transduction pathways in vascular cells and tissues. A major risk factor that promotes atherosclerosis is elevated oxidised low-density lipoprotein (oxLDL) particles, which is recognised by lectin-like oxLDL scavenger receptor 1 (LOX-1). LOX-1 is implicated in promoting atherosclerosis but the mechanism of action is unclear. To assess how LOX-1 signal transduction promotes disease outcomes, we used genetically engineered cell and animal models. We made a tetracycline-inducible endothelial cell line that expresses tagged wild-type human LOX-1. Stimulation of LOX-1-expressing endothelial cells with oxLDL causes increased signal transduction consistent with a role for LOX-1 in promoting inflammation and apoptosis. OxLDL binding stimulates LOX-1 endocytosis; however, LOX-1 undergoes efficient recycling from endosome-to-plasma membrane under stimulated and non-stimulated conditions. Although LOX-1-null transgenic mice displayed no obvious defects, LOX-1/ApoE-double null transgenic mice showed ~30% increase in atherosclerosis incidence compared to controls. Tissue analysis indicates that the presence of LOX-1 suppresses ERK1/2, p38 MAPK and NF-κB signal transduction. LOX-1 is thus an important link between dietary fats, pro-inflammatory signal transduction and atherosclerosis.

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