LOX-1 ELISA Kit, Mouse

BACKGROUND Lectin-like oxidized LDL receptor-1 (LOX-1) is a disulfide-linked homodimeric type II transmembrane protein with a short 34-residue cytoplasmic tail, a single transmembrane domain, and an extracellular region consisting of an 80-residue domain predicted to be a coil followed by a 130-residue C-terminal C-type lectin-like domain (CTLD) responsible for ox-LDL recognition. It belongs to the class E scavenger receptor family, a structurally diverse group of cell surface receptors of the innate immune system that recognize and internalize oxidized LDL (ox-LDL) in endothelial cells of large arteries. More recent studies have indicated that LOX-1 is expressed in other cells types, including macrophages, vascular smooth-muscle cells, and platelets. Its expression is not constitutive, but rather, markedly induced by proinflammatory, oxidative, and mechanical stimuli, which leads to the activation of endothelial cells, transformation of smooth-muscle cells, and accumulation of lipids in macrophages, resulting in cellular injury and the development of atherosclerosis.¹

It has been demonstrated that oxLDL-mediated activation triggers an endothelial LOX-1-linked signaling pathway leading to pro-inflammatory responses. LOX-1 activation stimulates ROS production and activates NF-κB. NF-κB activation and translocation into the nucleus results in increased transcription of genes encoding pro-inflammatory and adhesion molecules, e.g. tumor necrosis factor-α, ICAM-1, and VCAM-1. A different signaling pathway in vascular smooth muscle cells (VSMCs) may also be regulated by LOX-1 activation. VSMC differentiation, migration, and proliferation regulate the formation of the fibrous cap and ECM of atherosclerotic plaques. Moreover, LOX-1 activation by oxLDL stimulates the p38 MAPK intracellular signaling pathway, increasing endothelial MMP gene expression, secretion, and activity in vitro. The CD40-CD40L receptor-ligand system regulates this pathway in VSMCs by inducing pro-inflammatory gene expression including cytokines, proteinases, and adhesion molecules. Recent findings suggest that LOX-1 activation elevates the CD40-CD40L pathophysiological response in VSMCs. The shedding of endothelial membrane proteins as soluble fragments into extracellular fluids are potential vascular disease biomarkers.² Soluble circulatory polypeptides derived from adhesion proteins, e.g. VCAM-1 and ICAM-1, are generated by post-translational processing. LOX-1 also undergoes post-translational proteolytic cleavage within the “neck” region of the extracellular domain releasing a 187-residue polypeptide containing the C-type lectin-like domain known as sLOX-1. Mammalian sLOX-1 is a potentially exciting biomarker in vascular disease prediction. The generation of a wider range of antibody and ligand-based assays to monitor membrane-bound or sLOX-1 in the vascular tissues or in body fluids could allow better diagnosis of different vascular and pro-inflammatory diseases.³
 

REFERENCES  

1. Reiss, A.B. et al: Curr. Med. Chem. 16:2641-52, 2009
2. Dunn, S. et al: Biochem. J. 409:349-55, 2008
3. Mehta, J.L. & Li, D.: J. Am. Coll. Cardiol. 39:1429-35, 2002

 

 

ELISA Kits are based on standard sandwich enzyme-linked immunosorbent assay technology. Freshly prepared standards, samples, and solutions are recommended for best results.