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1.
Experimental & Molecular Medicine ; : 594-602, 2012.
Article Dans Anglais | WPRIM | ID: wpr-14963

Résumé

The incidence of cardiovascular disease is predicted to increase as the population ages. There is accumulating evidence that arginase upregulation is associated with impaired endothelial function. Here, we demonstrate that arginase II (ArgII) is upregulated in aortic vessels of aged mice and contributes to decreased nitric oxide (NO) generation and increased reactive oxygen species (ROS) production via endothelial nitric oxide synthase (eNOS) uncoupling. Inhibiting ArgII with small interfering RNA technique restored eNOS coupling to that observed in young mice and increased NO generation and decreased ROS production. Furthermore, enhanced vasoconstrictor responses to U46619 and attenuated vasorelaxation responses to acetylcholine in aged vasculature were markedly improved following siRNA treatment against ArgII. These results might be associated with increased L-arginine bioavailability. Collectively, these results suggest that ArgII may be a valuable target in age-dependent vascular diseases.


Sujets)
Animaux , Souris , Acide 15-hydroxy-11alpha,9alpha-(époxyméthano)prosta-5,13-diénoïque/pharmacologie , Vieillissement , Aorte/enzymologie , Arginase/génétique , Endothélium vasculaire/enzymologie , Induction enzymatique , Techniques de knock-down de gènes , Souris de lignée C57BL , Monoxyde d'azote/métabolisme , Nitric oxide synthase type III/métabolisme , Petit ARN interférent/génétique , Espèces réactives de l'oxygène/métabolisme , Régulation positive , Vasoconstriction/effets des médicaments et des substances chimiques
2.
The Korean Journal of Physiology and Pharmacology ; : 123-128, 2011.
Article Dans Anglais | WPRIM | ID: wpr-727892

Résumé

Caesalpinia sappan (C. sappan) is a medicinal plant used for promoting blood circulation and removing stasis. During a screening procedure on medicinal plants, the ethylacetate extract of the lignum of C. sappan (CLE) showed inhibitory activity on arginase which has recently been reported as a novel therapeutic target for the treatment of cardiovascular diseases such as atherosclerosis. CLE inhibited arginase II activity prepared from kidney lysate in a dose-dependent manner. In HUVECs, inhibition of arginase activity by CLE reciprocally increased NOx production through enhancement of eNOS dimer stability without any significant changes in the protein levels of eNOS and arginase II expression. Furthermore, CLE-dependent arginase inhibition resulted in increase of NO generation and decrease of superoxide production on endothelium of isolated mice aorta. These results indicate that CLE augments NO production on endothelium through inhibition of arginase activity, and may imply their usefulness for the treatment of cardiovascular diseases associated with endothelial dysfunction.


Sujets)
Animaux , Souris , Aorte , Arginase , Athérosclérose , Circulation sanguine , Caesalpinia , Maladies cardiovasculaires , Endothélium , Rein , Dépistage de masse , Monoxyde d'azote , Nitric oxide synthase type III , Plantes médicinales , Superoxydes
3.
Korean Journal of Anesthesiology ; : 622-628, 2009.
Article Dans Anglais | WPRIM | ID: wpr-213790

Résumé

BACKGROUND: Native low-density lipoprotein (nLDL) was one of the modifiable risk factors contributed directly to cardiovascular diseases development. We investigated that nLDL stimulation induced NADPH oxidase activation and superoxide production that was an important factor on human aortic smooth muscle cells (hAoSMC) proliferation. METHODS: Superoxide generation was recorded with fluorescent-staining of dihydroethidine or by measuring lucigenin-induced chemiluminescence for 5 minutes. We examined cell proliferation with 4[-3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) reagent and analyzed the change of gene expression by northern blot analysis. RESULTS: nLDL stimulation increased superoxide anion production in hAoSMC that confirmed through dihydroethidine staining and lucigenin-induced chemiluminescence methods. nLDL-induced proliferation abolished with preincubation of superoxide scavengers or NADPH oxidase inhibitor. NADPH as a substrate of NADPH oxidase increased superoxide generation in both nLDL-stimulated and unstimulated cell homogenate, which was completely blocked at the diphenylene iodinium (DPI)- or apocynin-pretreated hAoSMC homogenates. Furthermore, superoxide generation was only observed at the fraction of cellular precipitate, but not in soluble fraction. Expression of p22phox in mRNA level increased with nLDL treatment as early as 30 minutes and transfection of anti-sense oligonucleotide of p22phox completely abolished nLDL-induced proliferation of hAoSMC. CONCLUSIONS: The above results have shown that nLDL-induced proliferation in hAoSMC depends on superoxide production through NADPH oxidase activation.


Sujets)
Humains , Technique de Northern , Maladies cardiovasculaires , Prolifération cellulaire , Dicarbéthoxydihydrocollidine , Expression des gènes , Lipoprotéines , Luminescence , Muscles lisses , Myocytes du muscle lisse , NADP , NADPH oxidase , Facteurs de risque , ARN messager , Superoxydes , Transfection
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