Article Text

PDF
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

Abstract

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.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.