The LOX-1 scavenger receptor regulates the response of human aortic endothelial cells to physiological levels of MPO-oxidized LDL

Abstract

Cardiovascular disease as a result of atherosclerosis is a leading cause of death worldwide. Atherosclerosis is primarily caused by the dysfunction of vascular endothelial cells and the subendothelial accumulation of oxidized forms of low-density lipoprotein (LDL). Early observations have linked oxidized LDL effects in atherogenesis to the lectin like oxidized LDL (LOX-1) scavenger receptor. It was shown that LOX-1 is upregulated by many inflammatory mediators and proatherogenic stimuli including cytokines, reactive oxygen species (ROS), hemodynamic blood flow, high blood sugar level and most importantly modified forms of LDL. Oxidized LDL signaling pathways in atherosclerosis were first explored using copper oxidized LDL (Cuox-LDL). In our study, we used the more physiologically relevant model of LDL oxidation and showed, for the first time, that myeloperoxidase (MPO) modified LDL may affect human aortic endothelial cells (HAEC) function through the LOX-1 scavenger receptor. We hypothesize that myeloperoxidase modified low density lipoprotein (Mox-LDL) drives endothelial dysfunction (ED) and increases inflammation in endothelial cells through LOX-1 which provides an initial hint to the pathways that are initiated by MoxLDL during ED and the progression of the atherosclerotic disease.