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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1179.)
© 2001 American Heart Association, Inc.

Vascular Biology

4-Hydroxynonenal Prevents NO Production in Vascular Smooth Muscle Cells by Inhibiting Nuclear Factor-B–Dependent Transcriptional Activation of Inducible NO Synthase

Yoshiyuki Hattori; Sachiko Hattori; Kikuo Kasai

From the Department of Endocrinology and Metabolism, Dokkyo University School of Medicine, Mibu, Tochigi, Japan.

Correspondence to Dr Yoshiyuki Hattori, Department of Endocrinology and Metabolism, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan. E-mail yhattori{at}dokkyomed.ac.jp

Abstract—The role of lipid peroxidation products in atherogenesis was studied. We investigated whether 4-hydroxy-2-nonenal (HNE) modulates activation of the nuclear factor (NF)-B system or alters expression of the NF-B target gene product, inducible NO synthase (iNOS), in vascular smooth muscle cells (VSMCs) stimulated by lipopolysaccharide (LPS) in combination with interferon (IFN)- (LPS/IFN). NO production induced by LPS/IFN was dose-dependently inhibited by HNE. NF-B activation by LPS/IFN was inhibited by HNE in a dose-dependent manner. HNE significantly decreased LPS/IFN-stimulated proteolysis of IB-. iNOS promoter activity stimulated by LPS/IFN was also decreased by HNE dose-dependently. The treatment of VSMCs with LPS/IFN strongly stimulated iNOS mRNA and protein expression. The LPS/IFN-induced increases in iNOS mRNA and protein levels were dose-dependently decreased by HNE. Our data suggest that treatment with HNE blocks signaling events required for IB- degradation, thereby preventing NF-B activation. Inhibition of NF-B–regulated gene expression, especially modulation of NO production, may contribute to atherogenesis.

Key Words: 4-hydroxy-2-nonenal • nuclear factor-B • nitric oxide • vascular smooth muscle cells

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