title: LOX-1 and ROS, inseparable factors in the process of endothelial damage.
abstract: Lectin-like oxidized low-density lipoprotein (LOX-1) has been identified in endothelial cells as the main receptor of oxidized low-density lipoprotein (OxLDL). LOX-1 is upregulated in the presence of pathological conditions including atherosclerosis, hypertension, and diabetes because it acts as a mediator of "endothelial dysfunction". It promotes the generation of superoxide anion (O2(-)), the inhibition of nitric oxide (NO) production and the increment of endothelial adhesiveness to monocytes. Recently, it was reported that OxLDL, binding to LOX-1, determined a significant increase in the generation of reactive oxygen species (ROS), suggesting the involvement of signaling pathways such as mitogen-activated protein kinases (MAPKs). It is now generally accepted that ROS act indirectly on the modulation of LOX-1 expression because ROS oxidize native LDL. Moreover, LOX-1 activation per se may stimulate ROS generation. Accordingly, our findings showed that high levels of ROS can directly increase LOX-1 production in microvascular endothelial cells (HMEC-1). It has been reported that OxLDL, usually > 20 μg protein/ml, induced apoptosis in a variety of cell types. At low concentrations (< 5 μg protein/ml) OxLDL appears to be associated with cell proliferation and low levels of ROS-induced capillary tube formation in endothelial cells. Our data and those of the literature indicate the existence of a direct control of LOX-1 by ROS. Although ROS in large amounts clearly have detrimental effects on cell biology, small amounts of ROS could have a beneficial effect, suggesting its therapeutic potential for reducing ischemic tissue.
authors.affiliation: Fondazione CNR/Regione Toscana G. Monasterio , Pisa , Italy.
authors.forename: V
authors.initials: V
authors.lastname: Lubrano
authors.forename: S
authors.initials: S
authors.lastname: Balzan
mesh_terms: D000818:Animals; D042783:Endothelial Cells / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D051127:Scavenger Receptors, Class E / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D005609:Free Radicals; D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D017382:Reactive Oxygen Species; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein
keywords: Ox-LDL receptors; angiogenesis; endothelial function; free radicals; oxidative stress