The PPARγ ligand, rosiglitazone, reduces vascular oxidative stress and NADPH oxidase expression in diabetic mice

2007 ◽  
Vol 46 (6) ◽  
pp. 456-462 ◽  
Author(s):  
Jinah Hwang ◽  
Dean J. Kleinhenz ◽  
Heidi L. Rupnow ◽  
Adam G. Campbell ◽  
Peter M. Thulé ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Diabetic Mice ◽  
Vascular Oxidative Stress

scholarly journals Protective Role of Endogenous Kallistatin in Vascular Injury and Senescence by Inhibiting Oxidative Stress and Inflammation

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Julie Chao ◽  
Youming Guo ◽  
Lee Chao
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Nadph Oxidase ◽  
Vascular Injury ◽  
Oxidase Activity ◽  
Sirtuin 1 ◽  
Mouse Lung ◽  
Heparin Binding ◽  
Diabetic Mice ◽  
Nadph Oxidase Activity

Kallistatin was identified in human plasma as a tissue kallikrein-binding protein and a serine proteinase inhibitor. Kallistatin exerts pleiotropic effects on angiogenesis, oxidative stress, inflammation, apoptosis, fibrosis, and tumor growth. Kallistatin levels are markedly reduced in patients with coronary artery disease, sepsis, diabetic retinopathy, inflammatory bowel disease, pneumonia, and cancer. Moreover, plasma kallistatin levels are positively associated with leukocyte telomere length in young African Americans, indicating the involvement of kallistatin in aging. In addition, kallistatin treatment promotes vascular repair by increasing the migration and function of endothelial progenitor cells (EPCs). Kallistatin via its heparin-binding site antagonizes TNF-α-induced senescence and superoxide formation, while kallistatin’s active site is essential for inhibiting miR-34a synthesis, thus elevating sirtuin 1 (SIRT1)/eNOS synthesis in EPCs. Kallistatin inhibits oxidative stress-induced cellular senescence by upregulating Let-7g synthesis, leading to modulate Let-7g-mediated miR-34a-SIRT1-eNOS signaling pathway in human endothelial cells. Exogenous kallistatin administration attenuates vascular injury and senescence in association with increased SIRT1 and eNOS levels and reduced miR-34a synthesis and NADPH oxidase activity, as well as TNF-α and ICAM-1 expression in the aortas of streptozotocin- (STZ-) induced diabetic mice. Conversely, endothelial-specific depletion of kallistatin aggravates vascular senescence, oxidative stress, and inflammation, with further reduction of Let-7g, SIRT1, and eNOS and elevation of miR-34a in mouse lung endothelial cells. Furthermore, systemic depletion of kallistatin exacerbates aortic injury, senescence, NADPH oxidase activity, and inflammatory gene expression in STZ-induced diabetic mice. These findings indicate that endogenous kallistatin displays a novel role in protection against vascular injury and senescence by inhibiting oxidative stress and inflammation.

scholarly journals The Synergistic Effect of Valsartan and LAF237 [(S)-1-[(3-Hydroxy-1-Adamantyl)Ammo]acetyl-2-Cyanopyrrolidine] on Vascular Oxidative Stress and Inflammation in Type 2 Diabetic Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Min Shen ◽  
Dongdong Sun ◽  
Weijie Li ◽  
Bing Liu ◽  
Shenxu Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Combination Treatment ◽  
Fold Change ◽  
Diabetic Mice ◽  
Dpp Iv ◽  
Vascular Oxidative Stress ◽  
To Receive ◽  
Type 2 Diabetic

Aim. To investigate the combination effects and mechanisms of valsartan (angiotensin II type 1 receptor blocker) and LAF237 (DPP-IV inhibitor) on prevention against oxidative stress and inflammation injury in db/db mice aorta.Methods. Db/db mice (n=40) were randomized to receive valsartan, LAF237, valsartan plus LAF237, or saline. Oxidative stress and inflammatory reaction in diabetic mice aorta were examined.Results. Valsartan or LAF237 pretreatment significantly increased plasma GLP-1 expression, reduced apoptosis of endothelial cells isolated from diabetic mice aorta. The expression of NAD(P)H oxidase subunits also significantly decreased resulting in decreased superoxide production and ICAM-1 (fold change: valsartan : 7.5 ± 0.7,P<0.05; LAF237: 10.2 ± 1.7,P<0.05), VCAM-1 (fold change: valsartan : 5.2 ± 1.2,P<0.05; LAF237: 4.8 ± 0.6,P<0.05), and MCP-1 (fold change: valsartan: 3.2 ± 0.6, LAF237: 4.7 ± 0.8;P<0.05) expression. Moreover, the combination treatment with valsartan and LAF237 resulted in a more significant increase of GLP-1 expression. The decrease of the vascular oxidative stress and inflammation reaction was also higher than monotherapy with valsartan or LAF237.Conclusion. These data indicated that combination treatment with LAF237 and valsartan acts in a synergistic manner on vascular oxidative stress and inflammation in type 2 diabetic mice.

scholarly journals Endothelial SHIP2 Suppresses Nox2 NADPH Oxidase–Dependent Vascular Oxidative Stress, Endothelial Dysfunction, and Systemic Insulin Resistance

Diabetes ◽  
2017 ◽  
Vol 66 (11) ◽  
pp. 2808-2821 ◽  
Author(s):  
Nicole T. Watt ◽  
Matthew C. Gage ◽  
Peysh A. Patel ◽  
Hema Viswambharan ◽  
Piruthivi Sukumar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Endothelial Dysfunction ◽  
Nadph Oxidase ◽  
Systemic Insulin Resistance ◽  
Vascular Oxidative Stress

Electroacupuncture pretreatment inhibits NADPH oxidase-mediated oxidative stress in diabetic mice with cerebral ischemia

2014 ◽  
Vol 1573 ◽  
pp. 84-91 ◽  
Author(s):  
Fan Guo ◽  
Wenying Song ◽  
Tao Jiang ◽  
Lixin Liu ◽  
Feng Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Nadph Oxidase ◽  
Diabetic Mice

scholarly journals Adventitial NADPH oxidase‐4 in vascular oxidative stress (693.12)

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Arlinda Deng ◽  
Huy Nguyen ◽  
Michael Adams ◽  
Hui Di Wang
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Nadph Oxidase 4 ◽  
Vascular Oxidative Stress

scholarly journals Inhibition of Rac1 GTPase Decreases Vascular Oxidative Stress, Improves Endothelial Function, and Attenuates Atherosclerosis Development in Mice

2021 ◽  
Vol 8 ◽  
Author(s):  
Sebastian Zimmer ◽  
Philip Roger Goody ◽  
Matthias Oelze ◽  
Alexander Ghanem ◽  
Cornelius F. Mueller ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Macrophage Infiltration ◽  
Ros Production ◽  
Wild Type ◽  
Nadph Oxidase Activity ◽  
Rac1 Gtpase ◽  
Atherosclerosis Development ◽  
Vascular Oxidative Stress

Aims: Oxidative stress and inflammation contribute to atherogenesis. Rac1 GTPase regulates pro-oxidant NADPH oxidase activity, reactive oxygen species (ROS) formation, actin cytoskeleton organization and monocyte adhesion. We investigated the vascular effects of pharmacological inhibition of Rac1 GTPase in mice.Methods and Results: We treated wild-type and apolipoprotein E-deficient (ApoE−/−) mice with Clostridium sordellii lethal toxin (LT), a Rac1 inhibitor, and assessed vascular oxidative stress, expression and activity of involved proteins, endothelial function, macrophage infiltration, and atherosclerosis development. LT-treated wild-type mice displayed decreased vascular NADPH oxidase activity and ROS production. Therapeutic LT doses had no impact on behavior, food intake, body weight, heart rate, blood pressure, vascular and myocardial function, differential blood count, and vascular permeability. ApoE−/− mice were fed a cholesterol-rich diet and were treated with LT or vehicle. LT treatment led to decreased aortic Rac1 GTPase activity, NADPH oxidase activity and ROS production, but had no impact on expression and membrane translocation of NADPH oxidase subunits and RhoA GTPase activity. LT-treated mice showed improved aortic endothelium-dependent vasodilation, attenuated atherosclerotic lesion formation and reduced macrophage infiltration of atherosclerotic plaques. Concomitant treatment of cholesterol-fed ApoE−/− mice with LT, the specific synthetic Rac1 inhibitor NSC 23766 or simvastatin comparably reduced aortic Rac1 activity, NADPH oxidase activity, oxidative stress, endothelial dysfunction, atherosclerosis development, and macrophage infiltration.Conclusions: These findings identify an important role of the small GTPase Rac1 in atherogenesis and provide a potential target for anti-atherosclerotic therapy.

scholarly journals MO629XANTHINE OXIDASE INHIBITOR ATTENUATES RENAL OXIDATIVE STRESS AND ENDOTHELIAL DYSFUNCTION THROUGH THE INHIBITION OF VEGF-NADPH OXIDASES IN DIABETIC NEPHROPATHY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Yu Ah Hong ◽  
Keum-Jin Yang ◽  
Wonjung Choi ◽  
Yoon-Kyung Chang ◽  
Cheol Whee Park ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Nadph Oxidase ◽  
Kidney Diseases ◽  
Oxidase Inhibitor ◽  
Control Group ◽  
Diabetic Mice ◽  
Serum Cystatin C ◽  
Renal Hypertrophy ◽  
Diabetes Group

Abstract Background and Aims Xanthine oxidase (XO) is one of major source of reactive oxygen species, and a XO inhibitor, febuxostat has been reported to the protection of kidney diseases. We investigated whether febuxostat exerts renoprotective effects against diabetic nephropathy (DN). Method Eight-week Male C57BL/6 mice were divided into four groups: Control group (Cont), Febuxostat control group (FEB), streptozotocin treated group (STZ) and a febuxostat and STZ-treated diabetes group (STZ+FEB). STZ was used to induce diabetes (50 mg/kg/day, 5 days), and 5 mg/kg of febuxostat was treated to experimental mice for 8 weeks. Results STZ-treated diabetic mice were significantly decreased in serum and kidney XO levels, serum cystatin C and albuminuria by febuxostat treatment. Febuxostat treatment decreased renal hypertrophy and mesangial matrix expansion in STZ-treated diabetic mice. Febuxostat treatment suppressed the expression of vascular endothelial growth factor (VEGF)1 and 3, NADPH oxidase (NOX)1, 2, and 4, and the levels of their catalytic subunit mRNA in in STZ-treated diabetic mice. Febuxostat treatment was accompanied by the downregulation of Akt phosphorylation, followed by the suppression of transcription factor forkhead box O3a phosphorylation and the enhancement of endothelial nitric oxide synthase. Finally, febuxostat improved oxidative stress and resulted in decreased 8-hydroxy-2'-deoxyguanosine and kidney malondialdehyde levels, and increased superoxide dismutase activity in STZ-treated diabetic mice. Conclusions Febuxostat attenuated DN by modulating oxidative stress and endothelial function through VEGF–NADPH oxidase signaling pathway.

scholarly journals Short-term e-cigarette vapour exposure causes vascular oxidative stress and dysfunction: evidence for a close connection to brain damage and a key role of the phagocytic NADPH oxidase (NOX-2)

2019 ◽  
Vol 41 (26) ◽  
pp. 2472-2483 ◽  
Author(s):  
Marin Kuntic ◽  
Matthias Oelze ◽  
Sebastian Steven ◽  
Swenja Kröller-Schön ◽  
Paul Stamm ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Endothelial Function ◽  
Vascular Function ◽  
Flow Mediated Dilation ◽  
Markers Of Oxidative Stress ◽  
Underlying Mechanisms ◽  
Vascular Oxidative Stress

Abstract Aims Electronic (e)-cigarettes have been marketed as a ‘healthy’ alternative to traditional combustible cigarettes and as an effective method of smoking cessation. There are, however, a paucity of data to support these claims. In fact, e-cigarettes are implicated in endothelial dysfunction and oxidative stress in the vasculature and the lungs. The mechanisms underlying these side effects remain unclear. Here, we investigated the effects of e-cigarette vapour on vascular function in smokers and experimental animals to determine the underlying mechanisms. Methods and results Acute e-cigarette smoking produced a marked impairment of endothelial function in chronic smokers determined by flow-mediated dilation. In mice, e-cigarette vapour without nicotine had more detrimental effects on endothelial function, markers of oxidative stress, inflammation, and lipid peroxidation than vapour containing nicotine. These effects of e-cigarette vapour were largely absent in mice lacking phagocytic NADPH oxidase (NOX-2) or upon treatment with the endothelin receptor blocker macitentan or the FOXO3 activator bepridil. We also established that the e-cigarette product acrolein, a reactive aldehyde, recapitulated many of the NOX-2-dependent effects of e-cigarette vapour using in vitro blood vessel incubation. Conclusions E-cigarette vapour exposure increases vascular, cerebral, and pulmonary oxidative stress via a NOX-2-dependent mechanism. Our study identifies the toxic aldehyde acrolein as a key mediator of the observed adverse vascular consequences. Thus, e-cigarettes have the potential to induce marked adverse cardiovascular, pulmonary, and cerebrovascular consequences. Since e-cigarette use is increasing, particularly amongst youth, our data suggest that aggressive steps are warranted to limit their health risks.

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