Lectin-like Oxidized Low-Density Lipoprotein (LDL) Receptor (LOX-1): A Chameleon Receptor for Oxidized LDL

Abstract

LOX-1, one of the main receptors for oxLDL, is found mainly on the surface of endothelial cells. It is a multifacet 52 kDa type II transmembrane protein that structurally belongs to the C-type lectin family. It exists with short intracellular N-terminal and long extracellular C-terminal hydrophilic domains separated by a hydrophobic domain of 26 amino acids. LOX-1 acts like a bifunctional receptor either showing pro-atherogenicity by activating the NFκB-mediated down signaling cascade for gene activation of pro-inflammatory molecules or playing an atheroprotective agent by receptor-mediated uptake of oxLDL in the presence of an anti-inflammatory molecule like IL-10. Mildly, moderately, and highly oxidized LDL show their characteristic features upon LOX-1 activation and its ligand binding indenture. The polymorphic LOX-1 genes are intensively associated with increased susceptibility to myocardial diseases. The splicing variant LOX IN dimerizes with the native form of LOX-1 and protects cells from damage by oxidized LDL. In the developing field of regenerating medicine, LOX-1 is a potential target for therapeutic intervention.

Overexpression of scavenger receptor and infiltration of macrophage in epicardial adipose tissue of patients with ischemic heart disease and diabetes

“…LOX-1 is one of the main SRs for OxLDL [34–36]. Under physiological conditions, these receptors are almost undetectable, however, under exposure to several proinflammatory and proatherogenic stimuli, such as diabetes, hypertension, and dyslipidemia, they are overexpressed [35].…”

Siglec-5 is a novel marker of critical limb ischemia in patients with diabetes

“…Monocytes can adhere to vascular endothelial cells through the interaction of Siglec-5 with P-selectin glycoprotein ligand-1 or von Willebrand factor 27 , 31 , and are recruited to the blood vessel wall by deformation and chemotaxis, resulting in transformation into macrophages. Ox-LDL tends to bind to glycosylated agglutinin-like receptors and Siglec-5 glycosylation may be increased in diabetic environment, thereby facilitating the combination of Siglec-5 with Ox-LDL 32 , 33 . This interaction causes macrophages to develop into lipid-rich foam cells, thereby promoting the formation of atherosclerotic plaques.…”

Oleacein and Foam Cell Formation in Human Monocyte-Derived Macrophages: A Potential Strategy against Early and Advanced Atherosclerotic Lesions

“…LOX-1 is structurally different from other known oxLDL receptors, including class A and class B, and consists of four domains: a short N-terminal cytoplasmic domain, a transmembrane domain, a connecting neck domain and a lectin-like domain at the C-terminus. LOX-1 expression is induced by pro-inflammatory factors, such as homocysteine, PMA, TNFα and inflammatory cytokines, whereas the statins superoxide dismutase or PPARγ activator decrease LOX-1 expression [30][31][32]. It is known, that LOX-1 is absent in human monocytes but it is activated in macrophages with oxLDL, lysophosphatidylcholine (LPC), palmitic acids and glucose.…”