LOX-1, an endothelial receptor for oxidized LDL - Implications for induction of endothelium dysfunction in the pathogenesis of vascular diseases

LOX-1, Lectin-like oxidized LDL receptor-1 is the major receptor for oxidized LDL preferentially expressed in endothelial cells. LOX-1 is a 50 KD membrane glycoprotein that structurally belongs to C-type lectin family. It is highly expressed in the endothelium of arteries as well as vascular rich organs. LOX-1 is also inducibly expressed in differentiated macrophages and transformed smooth muscle cells. In cultured endothelial cells, the expression of LOX-1 is unregulated by TNF-alpha, phorbol esters, shear stress, and Ox-LDL. In vivo, LOX-1 has been shown to be inducibly expressed in the atherosclerotic regions, and upregulated in the aortas and veins of hypertensive states. The ligands specificity of LOX-1 included Ox-LDL, acetyl LDL, and multiple negatively charged phospholipids. Consistently, the LOX-1 expression cells will bind and phagocytose aged/apoptotic cells characterized by exposing negatively charged phosphatidylserine in the cell surface. Taken together, as an endothelial specific scavenger receptor, LOX-1 are responsible for removing circulating cellular debris and waste in the physiological conditions. However, recognizing and excessive insudatation of Ox-LDL by LOX-1 will induce endothelial dysfunction thus initiate atherogenesis. A further study of the molecular mechanisms underlying LOX-1 ligands-receptor interaction will provide insights into the pathogenesis of athersclerosis and and other vascular diseases.