Inhibition of inducible nitric oxide synthesis by oxidized lipoprotein(a) in a murine macrophage cell line.
Increased plasma levels of human lipoprotein(a) (Lp(a)) are highly correlated with the development of atherosclerotic lesions. During our study, we investigated the effects of native and hypochlorite oxidized lipoprotein(a) (ox-Lp(a)) on nitric oxide production by the inducible nitric oxide synthase (iNOS) in lipopolysaccharide/interferon stimulated mouse macrophages (J774A.1). Ox-Lp(a) (0-2 microg/ml) induces a dose dependent inhibition of inducible nitric oxide synthesis. iNOS protein expression showed a dose dependent reduction as revealed by immunoblotting when cells were incubated with increasing amounts of ox-Lp(a). Ox-Lp(a) decreases iNOS mRNA synthesis as shown by reverse transcription-polymerase chain reaction. Ox-Lp(a) induced iNOS inhibition might contribute to the development of atherosclerotic lesions by reducing the anti-atherogenic effects of nitric oxide.
Institute for Physiology, Schwarzspanierstrasse 17, 1090, Vienna, Austria. thomas.moeslinger@univie.ac.at
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Moeslinger
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Friedl
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Volf
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Brunner
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Koller
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Spieckermann
D000818:Animals; D001120:Arginine / Q000378:metabolism; D001161:Arteriosclerosis / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D015153:Blotting, Western; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006997:Hypochlorous Acid / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D017270:Lipoprotein(a) / Q000378:metabolism* / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D008070:Lipopolysaccharides; D017270:Lipoprotein(a); D012333:RNA, Messenger; D009569:Nitric Oxide; D006997:Hypochlorous Acid; D007371:Interferon-gamma; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse