Contribution of lectin-like oxidized low-density lipoprotein receptor-1 and LOX-1 modulating compounds to vascular diseases.

The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is the major receptor for binding and uptake of oxidized low-density lipoprotein (oxLDL) in endothelial cells. LOX-1 is also expressed in macrophages, smooth muscle cells and platelets. Following internalization of oxLDL, LOX-1 initiates a vicious cycle from activation of pro-inflammatory signaling pathways, thus promoting an increased reactive oxygen species formation and secretion of pro-inflammatory cytokines. LOX-1 plays a pivotal role in the development of endothelial dysfunction, foam cell and advanced lesions formation as well as in myocardial ischemia. Furthermore, it is known that LOX-1 plays a pivotal role in mitochondrial DNA damage, vascular cell apoptosis, and autophagy. A large number of studies provide evidence of a LOX-1's role in endothelial dysfunction, hypertension, diabetes, and obesity. In addition, novel insights into LOX-1 ligands and the activated signaling pathways have been gained. Recent studies have shown an interaction of LOX-1 with microRNA's, thus providing novel tools to regulate LOX-1 function. Because LOX-1 is increased in atherosclerotic plaques and contributes to endothelial dysfunction, several compounds were tested in vivo and in vitro to modulate the LOX-1 expression in therapeutic approaches.