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LOX-1 in cardiovascular diseases, future therapeutic perspectives

Abstract:

The low-density oxidized lipoprotein lectin-1 (LOX-1) receptor, also known as OLR-1, is a scavenger receptor (SR) class E, which mediates the absorption of LDL cholesterol in its oxidized form by vascular cells. LOX-1 is involved in endothelial dysfunction, monocyte adhesion, smooth muscle cell proliferation, migration and apoptosis, foam cell formation, platelet activation, and vascular endothelial instability, all critical events in the pathogenesis of atherosclerosis. LOX-1 contributes to atherosclerotic plaque instability and the ultimate clinical sequelae of endothelial rupture and potentially fatal cardiac tissue ischemia. There is currently no drug approved or in clinical development from LOX-1, due to its complex biological mechanisms not fully elucidated. Various therapies have been used to inhibit the action of LOX-1; drugs such as antioxidants, statins, natural anti-inflammatory agents, which act on its expression, but all with moderate efficacy. The administration of anti-LOX-1 antibodies has also been evaluated to inhibit atherosclerosis by decreasing cellular events. The design of drugs focused on the knowledge of LOX-1 signaling pathways and the application of biotechnological tools allow the development of new therapeutic targets based on the potential of monoclonal antibodies. With this background, the LOX-1 receptor represents an attractive therapeutic target for the treatment of human atherosclerotic diseases. Recent evidence indicates that action on this SR is a possible strategy for the treatment of vascular disease, exploring in this review its role and potential future applications in diagnosis and therapy.