OLR1

LOX-1 is a receptor protein which belongs to the C-type lectin superfamily. Its gene is regulated through the cyclic AMP signaling pathway. The protein binds, internalizes and degrades oxidized low-density lipoprotein.^{[citation needed]}

Normally, LOX-1 expression on endothelial cells is low, but tumor necrosis factor alpha, oxidized LDL, blood vessel shear stress, and other atherosclerotic stimuli substantially increase LOX-1 expression.^[8][10]

LOX-1 may be involved in the regulation of Fas-induced apoptosis. Oxidized LDL induces endothelial cell apoptosis through LOX-1 binding.^[7] Other ligands for LOX-1 include oxidized high-density lipoprotein, advanced glycation end-products, platelets, and apoptotic cells.^[7][10] The binding of platelets to LOX-1 causes a release of vasoconstrictive endothelin, which induces endothelial dysfunction.^[10]

This protein may play a role as a scavenger receptor.^[6]

Binding of oxidized LDL to LOX-1 activates NF-κB, leading to monocyte adhesion to enthothelial cells (a pre-requisite for the macrophage foam cell formation of atherosclerosis).^[8] Macrophage affinity for unmodified LDL particles is low, but is greatly increased when the LDL particles are oxidized.^[11] LDL oxidation occurs in the sub-endothelial space, rather than in the circulation.^[11] But oxidized cholesterol from foods cooked at high temperature can also be a source of oxysterols.^[9]

Mutations of the OLR1 gene have been associated with atherosclerosis, risk of myocardial infarction, and may modify the risk of Alzheimer's disease.^[6] When applied to human macrophage-derived foam cells in vitro, the dietary supplement berberine inhibits the expression of the ORL1 gene in response to oxidized low-density lipoprotein cholesterol,^[12] but this has not yet been demonstrated in a living animal or human.^{[citation needed]}