Oxidative stress and inflammation are central mediators of atherosclerosis particularly in the context of diabetes. The potential interactions between the major producers of vascular reactive oxygen species (ROS), NADPH oxidase (NOX) enzymes and immune-inflammatory processes remain to be fully elucidated. In the present study we investigated the roles of the NADPH oxidase subunit isoforms, NOX4 and NOX1, in immune cell activation and recruitment to the aortic sinus atherosclerotic plaque in diabetic ApoE−/− mice. Plaque area analysis showed that NOX4- and NOX1-derived ROS contribute to atherosclerosis in the aortic sinus following 10 weeks of diabetes. Immunohistochemical staining of the plaques revealed that NOX4-derived ROS regulate T-cell recruitment. In addition, NOX4-deficient mice showed a reduction in activated CD4+ T-cells in the draining lymph nodes of the aortic sinus coupled with reduced pro-inflammatory gene expression in the aortic sinus. Conversely, NOX1-derived ROS appeared to play a more important role in macrophage accumulation. These findings demonstrate distinct roles for NOX4 and NOX1 in immune-inflammatory responses that drive atherosclerosis in the aortic sinus of diabetic mice.
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GABAB receptor-mediated hypertension via hyperpolarization of solitary tract nucleus neurons that receive and integrate baroreceptor afferent inputs. See pp. 1417-1434 for further details. Image kindly provided by Omar Logue
Research Article|
June 29 2016
Differential effects of NOX4 and NOX1 on immune cell-mediated inflammation in the aortic sinus of diabetic ApoE−/− mice
Elyse Di Marco;
Elyse Di Marco
*Diabetic Complications Division, Baker IDI Heart & Diabetes Institute, Melbourne, Australia
†Department of Medicine, Monash University, Melbourne, Australia
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Stephen P. Gray;
Stephen P. Gray
*Diabetic Complications Division, Baker IDI Heart & Diabetes Institute, Melbourne, Australia
†Department of Medicine, Monash University, Melbourne, Australia
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Phyllis Chew;
Phyllis Chew
*Diabetic Complications Division, Baker IDI Heart & Diabetes Institute, Melbourne, Australia
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Kit Kennedy;
Kit Kennedy
*Diabetic Complications Division, Baker IDI Heart & Diabetes Institute, Melbourne, Australia
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Mark E. Cooper;
Mark E. Cooper
*Diabetic Complications Division, Baker IDI Heart & Diabetes Institute, Melbourne, Australia
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Harald H.H.W. Schmidt;
Harald H.H.W. Schmidt
‡Department of Pharmacology & Cardiovascular Research Institute Maastricht (CARIM), Faculty of Medicine, Health & Life Science, Maastricht University, The Netherlands
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Karin A.M. Jandeleit-Dahm
*Diabetic Complications Division, Baker IDI Heart & Diabetes Institute, Melbourne, Australia
†Department of Medicine, Monash University, Melbourne, Australia
Correspondence: Karin Jandeleit-Dahm (email Karin.jandeleit-dahm@bakeridi.edu.au).
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Publisher: Portland Press Ltd
Received:
December 22 2015
Revision Received:
May 14 2016
Accepted:
May 17 2016
Accepted Manuscript online:
May 17 2016
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society
2016
Clin Sci (Lond) (2016) 130 (15): 1363–1374.
Article history
Received:
December 22 2015
Revision Received:
May 14 2016
Accepted:
May 17 2016
Accepted Manuscript online:
May 17 2016
Citation
Elyse Di Marco, Stephen P. Gray, Phyllis Chew, Kit Kennedy, Mark E. Cooper, Harald H.H.W. Schmidt, Karin A.M. Jandeleit-Dahm; Differential effects of NOX4 and NOX1 on immune cell-mediated inflammation in the aortic sinus of diabetic ApoE−/− mice. Clin Sci (Lond) 1 August 2016; 130 (15): 1363–1374. doi: https://doi.org/10.1042/CS20160249
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