The Discovery of LOX-1, its Ligands and Clinical Significance

Abstract

LOX-1 is an endothelial receptor for oxidized low-density lipoprotein (oxLDL), a key molecule in the pathogenesis of atherosclerosis.The basal expression of LOX-1 is low but highly induced under the influence of proinflammatory and prooxidative stimuli in vascular endothelial cells, smooth muscle cells, macrophages, platelets and cardiomyocytes. Multiple lines of in vitro and in vivo studies have provided compelling evidence that LOX-1 promotes endothelial dysfunction and atherogenesis induced by oxLDL. The roles of LOX-1 in the development of atherosclerosis, however, are not simple as it had been considered. Evidence has been accumulating that LOX-1 recognizes not only oxLDL but other atherogenic lipoproteins, platelets, leukocytes and CRP. As results, LOX-1 not only mediates endothelial dysfunction but contributes to atherosclerotic plaque formation, thrombogenesis, leukocyte infiltration and myocardial infarction, which determine mortality and morbidity from atherosclerosis. Moreover, our recent epidemiological study has highlighted the involvement of LOX-1 in human cardiovascular diseases. Further understandings of LOX-1 and its ligands as well as its versatile functions will direct us to ways to find novel diagnostic and therapeutic approaches to cardiovascular disease.

Increased Levels of Lectin‐Like Oxidized Low‐Density Lipoprotein Receptor‐1 in Ischemic Stroke and Transient Ischemic Attack

“…However, although we found no significant correlation between plaque OLR1 mRNA levels and sLOX‐1 in plasma, lack of statistical correlations do not rule out any causal relationship. Indeed, the regulation of membrane‐bound LOX‐1 and its release into the circulation is modified by numerous stimuli, such as cytokines, modified lipoproteins, statins, and metalloproteinases 1, 3, 28, 29, 30. Therefore, it is not unlikely that there is a nonlinear relationship between plaque mRNA levels of OLR1 and the amounts of sLOX‐1 that are shed from the atherosclerotic lesions into the circulation.…”

“…In addition, different animal models have confirmed upregulation of OLR1 expression in the vasculature during inflammatory and oxidative conditions 30. However, the exploratory foundation of OLR1 expression in the human vasculature in vivo is rather scarce.…”

oxLDL induces injury and defenestration of human liver sinusoidal endothelial cells via LOX1

“…LOX1 is one of the major scavenger receptors (SRs) responsible for binding, internalising and degrading oxLDL (Sawamura et al 1997). LOX1 activation is associated with many pathophysiological events, including endothelial cell (EC) and vascular smooth muscle cell proliferation, alterations in cell cycle signals, apoptosis and autophagy (Zabirnyk et al 2010, Yoshimoto et al 2011. Accumulating evidence indicates that oxLDL binding to LOX1 increases intracellular reactive oxygen species (ROS), activates the NFkB signaling pathway, decreases intracellular nitric oxide (NO) and increases endothelin 1 (ET1), which could lead to endothelial dysfunction (Cominacini et al 2000, Morawietz et al 2002, Fleming et al 2005.…”

Protective effect of oleanolic acid on oxidized-low density lipoprotein induced endothelial cell apoptosis

“…First identified as an endothelial-specific scavenger receptor by Sawmura in 1997 (18), LOX-1 has been found to be expressed in endothelial cells, macrophages, vascular smooth muscle and platelets and can be upregulated by many factors such as ox-LDL, Ang II, shear stress, and advanced glycation (32)(33)(34). A number of studies implicated that the apoptosis of endothelial cells induced by ox-LDL was predominantly mediated by LOX-1 whose expression is strongly induced by exposure to ox-LDL (16,34).…”