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SHR Neuro Krebs Kardio Lipid

Marsche, G; Weigle, B; Sattler, W; Malle, E.
Soluble RAGE blocks scavenger receptor CD36-mediated uptake of hypochlorite-modified low-density lipoprotein.
FASEB J. 2007; 21(12): 3075-3082. [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Malle Ernst
Marsche Gunther
Sattler Wolfgang
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Number of Figures: 4
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Abstract:
Engagement of the receptor for advanced glycation end products (RAGE) by its signal transduction ligands evokes inflammatory cell infiltration and activation of the vessel wall. However, soluble RAGE (sRAGE), the truncated form spanning the extracellular binding domain of RAGE, has potent anti-inflammatory properties by acting as a decoy for RAGE ligands. We now show that sRAGE binds with high affinity to atherogenic low-density lipoprotein (LDL) modified by hypochlorous acid (HOCl), the major oxidant generated by the myeloperoxidase-H2O2-chloride system of phagocytes activated during inflammation. We further demonstrate that sRAGE can be coprecipitated with HOCl-LDL from spiked serum. To determine the functional significance of sRAGE binding to HOCl-LDL, cell association studies with macrophages were performed. sRAGE effectively inhibited cellular uptake of HOCl-LDL and subsequent lipid accumulation. Using Chinese hamster ovary cells overexpressing class B scavenger receptor CD36 or SR-BI, two preferential scavenger receptors for HOCl-LDL, we demonstrate that sRAGE only interferes with CD36-mediated uptake of HOCl-LDL. The present findings indicate that sRAGE acts as a sink for HOCl-LDL, which is abundantly present in human atherosclerotic lesions. We propose that sRAGE represents a physiological antagonist that interferes with scavenger receptor-mediated cholesterol accumulation and foam cell formation of macrophages.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Atherosclerosis - metabolism
Cell Line - metabolism
Cricetinae - metabolism
Cricetulus - metabolism
Glycosylation End Products, Advanced - metabolism
Humans - metabolism
Hypochlorous Acid - metabolism
Lipoproteins, LDL - metabolism
Macrophages - cytology
Mice - cytology
Oxidants - metabolism
Peptide Fragments - genetics
Protein Binding - genetics
Receptors, Immunologic - genetics
Scavenger Receptors, Class B - genetics

Find related publications in this database (Keywords)
myeloperoxidase
inflammation
oxidized LDL
foam cells
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