Targeting the LOX-1 scavenger receptor for therapeutics and diagnostics

Vascular dysfunction underpins major pathologies including cardiovascular disease, stroke and cancer. Lipid particle (LP) recognition, processing and metabolism impacts on vascular health and disease. Membrane proteins termed scavenger receptors (SRs) recognize modified LPs to mediate signaling, trafficking and processing in cells and tissues.

We explore the role of the lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1, OLR1) in pathophysiology including myocardial infarction, stroke, Type 2 diabetes and cancer. Oxidized LDL (oxLDL) activation of LOX-1 promotes cellular responses associated with cell dysfunction, highlighting this molecular target in disease prevention, therapy and diagnostics. Furthermore, we evaluate emerging therapeutic modalities including monoclonal antibodies, peptides, small molecules, and nucleic acid-based agents and consider the translational potential of LOX-1-targeted diagnostics, particularly in point-of-care settings.

Multiple lines of evidence indicate that LOX-1 expression and function is low or negligible during normal physiology; however, LOX-1 expression and signaling are elevated under pro-inflammatory conditions. LOX-1 signaling is associated with NF-kB activation, gene expression, cell proliferation and apoptosis. Blocking LOX-1-linked cellular responses has beneficial outcomes in pathophysiological states. The development of LOX-1-specific therapeutic and diagnostic agents, particularly those suitable for point-of-care use, represents a promising avenue for multi-disease intervention.