Homocysteine Increases Nitric Oxide Synthesis in Cytokine-Stimulated Vascular Smooth Muscle Cells

Ikeda, Uichi; Ikeda, Michiyo; Minota, Seiji; Shimada, Kazuyuki

doi:10.1161/01.cir.99.9.1230

Cited by 62 publications

(35 citation statements)

References 40 publications

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“…The present study applied homocysteine in doses up to millimolar concentrations (0.5-5 mM), which are comparable to those employed previously for in vitro studies (15)(16)(17). In accordance with these earlier studies, we established that homocysteine concentrations up to 5 mM had no significant effect on overall cell viability (18,19).…”

Section: Effects Of Homocysteine On Basal and Tnf-␣-mediated Surface supporting

confidence: 85%

Homocysteine Inhibits TNF-α-Induced Endothelial Adhesion Molecule Expression and Monocyte Adhesion via Nuclear Factor-κB Dependent Pathway

Stangl

Günther

Jarrin

et al. 2001

Biochemical and Biophysical Research Communications

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Section: Effects Of Homocysteine On Basal and Tnf-␣-mediated Surface supporting

confidence: 85%

Homocysteine Inhibits TNF-α-Induced Endothelial Adhesion Molecule Expression and Monocyte Adhesion via Nuclear Factor-κB Dependent Pathway

Stangl

Günther

Jarrin

et al. 2001

Biochemical and Biophysical Research Communications

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“…This has been proposed to account for the benefits of an argininesupplemented diet on atherosclerosis in animal models of the disease, even though arginine is not thought to be limiting in the plasma. In addition, a known risk factor for the development of atherosclerosis, homocysteine, induces iNOS transcription in vascular smooth muscle cells in vitro (45,46). Thus the potential for tissue destruction exists at sites where iNOS is expressed.…”

Section: Discussionmentioning

confidence: 99%

Deficiency in Inducible Nitric Oxide Synthase Results in Reduced Atherosclerosis in Apolipoprotein E-Deficient Mice

Detmers

Hernandez

Mudgett

et al. 2000

The Journal of Immunology

191

132

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Inducible NO synthase (iNOS) present in human atherosclerotic plaques could contribute to the inflammatory process of plaque development. The role of iNOS in atherosclerosis was tested directly by evaluating the development of lesions in atherosclerosis-susceptible apolipoprotein E (apoE)−/− mice that were also deficient in iNOS. ApoE−/− and iNOS−/− mice were cross-bred to produce apoE−/−/iNOS−/− mice and apoE−/−/iNOS+/+ controls. Males and females were placed on a high fat diet at the time of weaning, and atherosclerosis was evaluated at two time points by different methods. The deficiency in iNOS had no effect on plasma cholesterol, triglyceride, or nitrate levels. Morphometric measurement of lesion area in the aortic root at 16 wk showed a 30–50% reduction in apoE−/−/iNOS−/− mice compared with apoE−/−/iNOS+/+ mice. Although the size of the lesions in apoE−/−/iNOS−/− mice was reduced, the lesions maintained a ratio of fibrotic:foam cell-rich:necrotic areas that was similar to controls. Biochemical measurements of aortic cholesterol in additional groups of mice at 22 wk revealed significant 45–70% reductions in both male and female apoE−/−/iNOS−/− mice compared with control mice. The results indicate that iNOS contributes to the size of atherosclerotic lesions in apoE-deficient mice, perhaps through a direct effect at the site of the lesion.

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“…All other immunoblotting with an anti-iNOS antibody as described chemicals used were of the highest grade commercially previously [27]. Peroxidase-labeled proteins were detected available.…”

Section: Methodsmentioning

confidence: 99%

C-Reactive protein augments inducible nitric oxide synthase expression in cytokine-stimulated cardiac myocytes

Ikeda

Maeda

Yamamoto

et al. 2002

Cardiovascular Research

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Objective: Nitric oxide (NO) production by inducible NO synthase (iNOS) can exert negative inotropic and cytotoxic effects on cardiac myocytes and may play an important role in the pathogenesis of cardiac dysfunction and remodeling. An elevated serum level of C-reactive protein (CRP) is an important predictive factor for cardiac disorders including acute myocardial infarction and dilated cardiomyopathy. The basic mechanisms responsible for this association are not clear; CRP may merely be a marker of inflammation with no specific role in the pathogenesis of cardiac disease or may directly modulate the disease process. We investigated the effects of CRP on iNOS expression and subsequent NO synthesis in rat cardiac myocytes, and the mechanism by which CRP exerts its effects. Methods: NO production by culture neonatal rat cardiac myocytes was determined by measurement of nitrite contents in the culture medium. The expression of iNOS mRNA and protein were measured by reverse transcription-polymerase chain reaction and Western blotting, respectively. The levels of nuclear factor (NF)-kB proteins were analyzed by a gel retardation assay. Results: Incubation of cardiac myocytes with interleukin-1b (IL-1b; 10 ng / ml) caused a significant increase in nitrite production. CRP significantly increased the IL-1b-induced nitrite production in a dose-dependent manner (10-100 mg / ml). Incubation with IL-1b induced the expression of iNOS mRNA and protein in cardiac myocytes, and CRP enhanced their expression. Addition of IL-1b activated NF-kB in cardiac myocytes, while CRP did not affect IL-1b-induced NF-kB activation. Conclusions: These results indicated that CRP directly enhances NO synthesis in IL-1b-stimulated cardiac myocytes through an NF-kB-independent mechanism. 

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Homocysteine Increases Nitric Oxide Synthesis in Cytokine-Stimulated Vascular Smooth Muscle Cells

Cited by 62 publications

References 40 publications

Homocysteine Inhibits TNF-α-Induced Endothelial Adhesion Molecule Expression and Monocyte Adhesion via Nuclear Factor-κB Dependent Pathway

Homocysteine Inhibits TNF-α-Induced Endothelial Adhesion Molecule Expression and Monocyte Adhesion via Nuclear Factor-κB Dependent Pathway

Deficiency in Inducible Nitric Oxide Synthase Results in Reduced Atherosclerosis in Apolipoprotein E-Deficient Mice

C-Reactive protein augments inducible nitric oxide synthase expression in cytokine-stimulated cardiac myocytes

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