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      LOX-1, the receptor for oxidized low-density lipoprotein identified from endothelial cells: implications in endothelial dysfunction and atherosclerosis

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      Pharmacology & Therapeutics
      Elsevier BV

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          Abstract

          Lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) was initially identified as the major receptor for oxidized LDL (OxLDL) in endothelial cells. Its inducible expression in macrophages and smooth muscle cell was also observed. LOX-1 is a Type II membrane protein with a typical C-type lectin structure at the extracellular C-terminus. It can be cleaved by an unknown protease at the extracellular juxtamembrane region to release the soluble form of LOX-1. The extracellular domains of LOX-1 are post-translationally modified by N-linked glycosylation. Mutagenesis studies revealed that the lectin domain of LOX-1 is the functional domain that recognizes the LOX-1 ligand. The C-terminal end residues and several conserved positively charged residues spanning the lectin domain are essential for OxLDL binding. LOX-1 activation by OxLDL causes endothelial changes that are characterized by activation of nuclear factor-kappaB through an increased reactive oxygen species, subsequent induction of adhesion molecules, and endothelial apoptosis. In vitro, expression of LOX-1 is induced by many inflammatory cytokines, oxidative stress, hemodynamic stimuli, and OxLDL. In vivo, the expression is enhanced in pro-atherogenic settings including, hypertension, hyperlipidemia, and diabetes, and, indeed, is accumulated in the atherosclerotic and glomerulosclerotic lesions. LOX-1 binds multiple classes of ligands that are implicated in the pathogenesis of atherosclerosis. Besides OxLDL, LOX-1 can recognize apoptotic/aged cells, activated platelets, and bacteria, implying versatile physiological functions. Taken together, all these findings support the possible contribution of LOX-1 to the pathogenesis of vascular disorders, particularly atherosclerosis. Development of antagonists for LOX-1 might be a good therapeutic approach to vascular diseases.

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          Author and article information

          Journal
          Pharmacology & Therapeutics
          Pharmacology & Therapeutics
          Elsevier BV
          01637258
          July 2002
          July 2002
          : 95
          : 1
          : 89-100
          Article
          10.1016/S0163-7258(02)00236-X
          12163130
          cbd591ba-e7ac-4849-8a78-482c774624ac
          © 2002

          https://www.elsevier.com/tdm/userlicense/1.0/

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