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Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a type II transmembrane glycoprotein that serves as the principal receptor for oxidized LDL (oxLDL) in vascular endothelial cells [UniProt P78380]. Encoded by the OLR1 gene, it belongs to the C-type lectin-like superfamily and functions as a class E scavenger receptor [PubMed PMID: 9052785]. Under physiological conditions, LOX-1 expression is minimal, but it is rapidly induced by pro-inflammatory cytokines, mechanical stretch, and oxidative stress [PubMed PMID: 28611102]. The binding of oxLDL to LOX-1 triggers downstream signaling cascades, such as the NF-κB and MAPK pathways, which promote endothelial dysfunction, leukocyte adhesion, and foam cell formation [PubMed PMID: 31430566]. Consequently, LOX-1 is a critical mediator in the pathogenesis of atherosclerosis, myocardial infarction, and stroke [PubMed PMID: 24508244]. Beyond cardiovascular disease, LOX-1 is implicated in cancer progression and inflammation-related disorders [PubMed PMID: 25100373]. Therapeutic interventions currently under investigation include monoclonal antibodies like BI 765179 and small molecules that block the receptor's ligand-binding domain [ClinicalTrials.gov NCT04167969]. Additionally, the proteolytic cleavage of the extracellular domain produces soluble LOX-1 (sLOX-1), which serves as a diagnostic biomarker for acute coronary syndromes [PubMed PMID: 21444838].
Direct inhibition of oxidized LDL binding to the C-type lectin-like domain and indirect downregulation of receptor expression via modulation of inflammatory pathways.
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