{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nOLR1, which encodes the lectin‐like oxidized low‐density lipoprotein (oxLDL) receptor (LOX‑1), functions as a multifunctional scavenger receptor expressed prominently on vascular endothelial cells, macrophages, dendritic cells, and other cell types. By binding modified lipoproteins (including oxLDL, electronegative LDL, and even endogenous ligands such as heat shock proteins, C‑reactive protein, and phosphatidylserine), LOX‑1 triggers intracellular signal transduction cascades. These pathways, involving reactive oxygen species generation, NF‑κB activation, alterations in Akt and MAPK phosphorylation, and cytoskeletal changes, promote endothelial dysfunction, foam cell formation, and plaque progression in atherosclerosis. In addition, LOX‑1 activation contributes to apoptotic and autophagic responses that further destabilize vascular integrity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its classical role in lipid uptake and vascular injury, LOX‑1 also modulates immune and inflammatory responses. Its expression on dendritic cells enhances antigen cross‐presentation and CD8⁺ T‑cell priming, thereby contributing to antitumor immunity, while its presence on platelets and B cells influences integrin activation, cell adhesion and migration. Moreover, the receptor’s activity is tightly regulated by factors such as microRNAs (e.g. let‑7 family) and naturally occurring splice variants (eg, LOXIN), and its plasma membrane localization is dependent on cholesterol‑rich raft integrity—features that have significant therapeutic implications."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "23", "end_ref": "32"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nClinical and genetic investigations further underscore the importance of LOX‑1 in human disease. Distinctions between LOX‑1 and related molecules such as lysyl oxidase (which modulates extracellular matrix stiffening) help clarify its unique contribution to atherogenesis. Specific genetic variants (for example, the G501C single nucleotide polymorphism) and soluble forms of the receptor have been associated with increased myocardial infarction risk and serve as biomarkers in conditions ranging from diabetes and obesity to preeclampsia. Collectively, these findings position OLR1/LOX‑1 as a central node in the interplay between lipid metabolism, oxidative stress, and immune regulation—making it a promising target for therapeutic intervention in cardiovascular disease, metabolic disorders, and cancer."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "33", "end_ref": "46"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yves Delneste, Giovanni Magistrelli, Jean Gauchat, et al. 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