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 correlat ed with the development of atherosclerotic lesions. During our study, we in vestigated 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 (J774 A.1). Ox-Lp(a) (0-2 mu g/ml) induces a dose dependent inhibition of inducib le nitric oside synthesis. iNOS protein expression showed a dose dependent reduction as revealed by immunoblotting when cells were incubated with incr easing amounts of ox-Lp(a). Ox-Lp(a) decreases iNOS mRNA synthesis as shown by reverse transcription-polymerase chain reaction. Os-Lp(a) induced iNOS inhibition might contribute to the development of atherosclerotic lesions b y reducing the antiatherogenic effects of nitric oxide. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.