Cholesterol level regulates lectin-like oxidized low-density lipoprotein receptor-1 function

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), the primary receptor for ox-LDL in endothelial cells, is a multi-ligand scavenger receptor that plays a crucial role in the pathogenesis of atherosclerosis and cardiovascular disorders and recently identified as a tumor marker. LOX-1 is naturally present in caveolae/lipid rafts in plasma membranes and disruption of these membrane domains by cholesterol-lowering drugs leads to a spatial disorganization of LOX-1 and a marked loss of specific LOX-1 function in terms of ox-LDL binding and internalization. Moreover, cholesterol depletion triggers the release of LOX-1 in exosomes and enhances shedding of LOX-1 ectodomain. We here provide an overview of the involvement of membrane and circulating cholesterol in LOX-1 function and shedding and its impact on cardiovascular pathologies and cancer. In particular, we consider the available biological and molecular evidence indicating LOX-1 as a potential therapeutic target for atherosclerosis, inflammation processes, myocardial infarction and cholesterol-lowering drugs as specific inhibitors of LOX-1 function.