Inducible nitric oxide synthase colocalizes with signs of lipid oxidation/peroxidation in human atherosclerotic plaques

Cromheeke, Kristel M.; Kockx, Mark; Meyer, Guido R.Y. De; Bosmans, Johan; Bult, Hidde; Beelaerts, W.; Vrints, C.; Herman, Arnold G.

doi:10.1016/s0008-6363(99)00148-0

Cited by 111 publications

(72 citation statements)

References 32 publications

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“…This is paralleled with the decreased mRNA and protein expression for eNOS and iNOS, suggesting that LDL treatment resulted in a transcriptional down-regulation of NOS mRNA and protein expression that led to the decreased NO-mediated endothelium-dependent vasodilation. As an important endothelium-derived signal mediator, NO plays key roles in vasodilation (Schulz et al, 2008) and cardiovascular disease pathogenesis (Cromheeke et al, 1999). A report showed that atherosclerotic lesions containing foam cells were induced in a model of atherosclerosis in rabbits with moderate hypercholesterolaemia by chronic inhibition of NOS (Kitahara et al, 2010), revealing the importance of NO system in the progression of atherosclerotic diseases.…”

Section: Discussionmentioning

confidence: 99%

Apolipoprotein B of low-density lipoprotein impairs nitric oxide-mediated endothelium-dependent relaxation in rat mesenteric arteries

Zhang

Edvinsson

et al. 2014

European Journal of Pharmacology

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Section: Discussionmentioning

confidence: 99%

Apolipoprotein B of low-density lipoprotein impairs nitric oxide-mediated endothelium-dependent relaxation in rat mesenteric arteries

Zhang

Edvinsson

et al. 2014

European Journal of Pharmacology

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“…The intensities of bands were analyzed by Quality One Image software (BioRad). The eNOS and iNOS mRNA levels were normalized to the ␤-actin mRNA signal (40). Western blotting and NO synthase activity.…”

Section: Methodsmentioning

confidence: 99%

Compromised Arterial Function in Human Type 2 Diabetic Patients

et al. 2005

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Diabetes is associated with a perturbation of signaling pathways in vascular tissue, which causes vasomotor dysfunction such as hypertension and accelerated atherosclerosis. In the present study, the mechanisms of vasomotor dysfunction, Akt (Thr 308 and Ser 473 ) phosphorylation and expression of endothelial NO (nitric oxide) synthase, and inducible NO synthase were investigated in human diabetic internal mammary arteries. The phospho-Akt (Thr 308 ) level in arteries from diabetic patients was reduced to about one-half of the level in nondiabetic patients, suggesting impaired insulin signaling in human diabetic vascular tissue. Augmented vasoconstriction was observed in diabetic arteries, due in part to deficiency of basal and stimulated NO production. This correlated with decreased endothelial NO synthase expression and activity in diabetic vessels. The sensitivity of diabetic vessels to the NO donor, sodium nitroprusside, was reduced as well, suggesting that NO breakdown and/or decreased sensitivity of smooth muscle to NO are also responsible for abnormal vasoconstriction. In addition, the abnormal vasoconstriction in diabetic vessels was not completely abolished in the presence of N-nitro-L-arginine methyl ester, revealing that NO-independent mechanisms also contribute to vasomotor dysfunction in diabetes. In conclusion, diabetes downregulates the Akt-signaling pathway and compromises human arterial function through a decrease in NO availability as well as through NO-independent mechanisms. Diabetes 54:2415-2423, 2005

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“…During the process of atherosclerosis development, the endothelial function is impaired. Therefore, the endothelium-derived cNOS expression or activity as well as the production of endothelial NO is decreased, whereas the activity of vascular smooth muscle cell (VSMC)-expressed iNOS is increased,11,12 resulting in increased NO free-radical production, which stimulates cell apoptosis and collagen degradation and promotes the development of atherosclerosis 11,13. NO free radicals could also synthesise peroxynitrite through a reaction with superoxide anion, thus causing further tissue damage 12…”

Section: Discussionmentioning

confidence: 99%

Effect of the haeme oxygenase-1/endogenous carbon monoxide system on atherosclerotic plaque formation in rabbits

Liu¹,

Fang²,

Wu³

et al. 2010

CardioVascular Journal of Africa

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ObjectiveTo investigate the effect of the haeme oxygenase-1/carbon monoxide (HO-1/CO) system on atherosclerotic plaque formation and its possible mechanism.MethodsFor 12 weeks, rabbits were given a 1.5% cholesterol diet (Ch group, n = 8) or a 1.5% cholesterol diet plus an HO-1 inducer, haemin (Hm group, n = 8), or an HO-1 inhibitor, zinc protoporphyrin IX (Znpp-IX, Zn group, n = 8) by intraperitoneal injection.ResultsCompared with the normal control group (C group, n = 8), serum levels of lipids and oxidised low-density lipoproteins (ox-LDL) increased significantly in all experimental groups (p < 0.01). However, no significant differences were observed among the three experimental groups (p > 0.01). Compared with the control group, aortic nitric oxide (NO) production and nitric oxide synthase (cNOS) activity decreased markedly, whereas carbon monoxide (CO) production and HO-1 activity increased markedly in the Ch group (p < 0.01). This was associated with an increase in the area of aortic plaque of 54.00 ± 4.16%. Compared with the Ch group, CO production and HO-1 activity increased markedly, while aortic HO activity and CO production decreased significantly in the Hm group. The area of aortic plaque was significantly reduced in the Hm group (17.88 ± 3.01%), whereas the area of aortic plaque was significantly increased in the Zn group (61.13 ± 3.50%). Compared with the Ch group, aortic endothlin-1 expression in the Hm group reduced significantly, while in the Zn group it was significantly higher than in the Ch group (p < 0.01).ConclusionThe HO-1/CO system plays an inhibitory role in atherosclerotic plaque formation. This role was not mediated by regulating serum lipids and ox-LDL, but was related to the reciprocal relationship between the HO-1/CO and NOS/NO systems in atherosclerosis and the down-regulated expression of endothlin-1 (ET-1), which inhibits the proliferation of vascular smooth muscle cells.

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Inducible nitric oxide synthase colocalizes with signs of lipid oxidation/peroxidation in human atherosclerotic plaques

Abstract: Ceroid, nitrotyrosine and NOS II colocalized in late stages of atherosclerosis and were found around the necrotic core in the plaque. This could suggest that NOS II expression in macrophages is involved in oxidation and peroxidation of lipids, leading to ceroid formation.

Cited by 111 publications

References 32 publications

Apolipoprotein B of low-density lipoprotein impairs nitric oxide-mediated endothelium-dependent relaxation in rat mesenteric arteries

Apolipoprotein B of low-density lipoprotein impairs nitric oxide-mediated endothelium-dependent relaxation in rat mesenteric arteries

Compromised Arterial Function in Human Type 2 Diabetic Patients

Effect of the haeme oxygenase-1/endogenous carbon monoxide system on atherosclerotic plaque formation in rabbits

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