Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf
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Hypochlorite-induced oxidation of low-density lipoproteins and high-density lipoprotein modifies their potential role in atherogenesisKopprasch, S.; Grässler, J.; Pietzsch, J.
Substantial evidence has accumulated that the myeloperoxidase (MPO)/hydrogen peroxide/hypochlorite system of phagocytes plays a critical role not only in antimicrobial defence but also in chronic inflammatory conditions like atherosclerosis. Oxidation of low-density lipoproteins (LDL) by hypochlorite (OCl-LDL) results in physico-chemical modifications of both the protein and lipid moiety of the lipoprotein molecule. Following oxidation OCl-LDL display a number of proatherogenic and proinflammatory properties including stimulation of phagocyte oxidant generation, induction of leukocyte degranulation, and increase of phagocyte adhesion to endothelial cells. Importantly, the class B scavenger receptors CD36 and SR-BI are receptors for OCl-LDL. This fact may explain the high uptake of OCl-LDL in macrophages, leading to the formation of foam cells. Our investigations revealed that OCl-LDL upregulates the gene expression of CD36 and PPAR in macrophages dose- and time-dependently while modulating SR-BI expression differently in dependence on incubation conditions. The antiatherogenic properties of high-density lipoproteins (HDL) are suggested to be mainly associated with its SR-BI-mediated reverse cholesterol transport. In addition we could demonstrate that HDL possesses anti-inflammatory actions by inhibiting OCl-LDL-induced increase in phagocyte respiratory burst and adhesion to endothelial cells. The protective role of HDL was substantially attenuated when HDL apolipoproteins were oxidized by hypochlorite. Our in vitro data show that hypochlorite-oxidized lipoproteins could mimic fundamental atherogenic and inflammatory processes therefore underlying the potential role of hypochlorite oxidation as pathogenetic factor in vivo.
Contribution to external collection
Pietzsch, J.: Protein Oxidation and Disease, Recent Research Developments in Pathological Biochemistry 1, Trivandrum, Kerala, India: Research Signpost, 2006, 81-308-0028-4, 179-196