TY - JOUR T1 - P46 Oxidisedoxidized LDL and LOX-1 scavenger receptor regulation of pro-atherogenic signal transduction JF - Heart JO - Heart SP - A16 LP - A16 DO - 10.1136/heartjnl-2016-310696.50 VL - 102 IS - Suppl 8 AU - I Abdul Zani AU - N Mughal AU - S Wheatcroft AU - S Ponnambalam Y1 - 2016/10/01 UR - http://heart.bmj.com/content/102/Suppl_8/A16.2.abstract N2 - 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. ER -