title: LOX-1:  a multiligand receptor at the crossroads of response to danger signals.
abstract: OBJECTIVE
  LOX-1 is a multiligand receptor implicated in endothelial dysfunction and atherosclerosis, although it was originally identified as an oxidized LDL receptor. In this review, the roles of various LOX-1 ligands and their interaction with LOX-1 are discussed to understand the pathophysiological significance of LOX-1.
  
  
  RESULTS
  LOX-1 knockout mice showed resistance of endothelium-dependent vasorelaxation against oxidized LDL and retardation of atherosclerosis progression. LOX-1 ligand reduction in mice also attenuated atherosclerosis progression. In a human cohort study, high concentration of apoB-containing LOX-1 ligands predicted the incidence of cardiovascular disease. Furthermore, modified HDL, which existed in high concentration in the plasma of coronary artery disease patients, was found to induce impairment of endothelial nitric oxide release via LOX-1. In addition to lipoproteins, LOX-1 was found to work as a C-reactive protein receptor providing a scaffold for the activation of the complement system.
  
  
  CONCLUSIONS
  LOX-1 is a unique molecule among the sensors of danger signals. LOX-1 is not only sensing danger signals such as modified LDL and heat shock protein, but also scaffolding other danger sensors including C-reactive protein and C1q, and directly commanding responses to danger signals by working as a cell adhesion molecule. Via these functions, LOX-1 might work as a surveillance molecule of vascular homeostasis.
authors: Department of Vascular Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan. t-sawamura@umin.ac.jp
authors: Tatsuya
authors: T
authors: Sawamura
authors: Akemi
authors: A
authors: Kakino
authors: Yoshiko
authors: Y
authors: Fujita
mesh_terms: D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism; D001161:Arteriosclerosis / Q000503:physiopathology*; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000503:physiopathology; D003167:Complement Activation; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D051131:Receptors, Oxidized LDL / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D001055:Apolipoproteins B; D008024:Ligands; C495137:OLR1 protein, human; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; D002097:C-Reactive Protein