Lectin-like oxidized LDL receptor-1: Its diverse roles beyond an oxidized LDL receptor and clinical relevance

Oxidative stress induced by reactive oxygen species (ROS) plays an important role in the pathogenesis of various cardiovascular diseases. The redox state is determined by the balance between the pro-oxidative and anti-oxidative systems, and its imbalance leads to oxidative stress. ROS directly induces endothelial injury and inactivates endotheliumderived nitric oxide, which is a potent protective factor for cardiovascular system. Furthermore, the oxidative Correspondence/Reprint request: Dr. Nobutaka Inoue, Department of Vascular Physiology, National Cardiovascular Center Research Institute, 5-7-1, Fujishirodai, Suita City, Osaka 565-8565, Japan E-mail: [email protected] Nobutaka Inoue & Tatsuya Sawamura 166 modification of low-density lipoprotein (LDL) by ROS is involved in atherogenesis through various mechanisms. For example, oxidized LDL induces endothelial dysfunction, expression of adhesion molecules and apoptosis of vascular smooth muscle cells. It has become evident that these cellular responses induced by oxidized LDL are mediated by lectin-like oxidized LDL receptor-1 (Lox-1). Lox-1 was identified from cultured aortic endothelial cells as a novel receptor for oxidized LDL. It has a type II membrane protein structure with a short N-terminal cytosolic domain and a long C-terminal extracellular domain. Lox-1 is expressed in not only endothelial cells but also various cell types including smooth muscle cells, and its expression is dynamically regulated. Recent progress in the research of Lox-1 has brought novel concepts with regard to its functional significance and biological activities. It has become evident that beside oxidized LDL, Lox-1 recognizes multiple ligands including apoptotic cells, platelets, advanced glycation end products, heat shock protein, and bacteria. Furthermore, recent investigations revealed that Lox-1 plays a central role in the host-defense system and inflammatory responses, and it is involved in the pathogenesis of various diseases such as atherosclerosis, septic shock, vascular remodeling, and acute coronary syndrome. Given the potent and wide variety of biological activities, the approach to modify the Lox-1-mediated pathway might be a potential therapeutic strategy for various diseases.