title: Differential effects of NOX4 and NOX1 on immune cell-mediated inflammation in the aortic sinus of diabetic ApoE-/- mice.
abstract: 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.
authors.affiliation: Diabetic Complications Division, Baker IDI Heart & Diabetes Institute, Melbourne, Australia Department of Medicine, Monash University, Melbourne, Australia.
authors.forename: Elyse
authors.initials: E
authors.lastname: Di Marco
authors.affiliation: Diabetic Complications Division, Baker IDI Heart & Diabetes Institute, Melbourne, Australia Department of Medicine, Monash University, Melbourne, Australia.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Gray
authors.affiliation: Diabetic Complications Division, Baker IDI Heart & Diabetes Institute, Melbourne, Australia.
authors.forename: Phyllis
authors.initials: P
authors.lastname: Chew
authors.affiliation: Diabetic Complications Division, Baker IDI Heart & Diabetes Institute, Melbourne, Australia.
authors.forename: Kit
authors.initials: K
authors.lastname: Kennedy
authors.affiliation: Diabetic Complications Division, Baker IDI Heart & Diabetes Institute, Melbourne, Australia.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Cooper
authors.affiliation: Department of Pharmacology & Cardiovascular Research Institute Maastricht (CARIM), Faculty of Medicine, Health & Life Science, Maastricht University, The Netherlands.
authors.forename: Harald H H W
authors.initials: HH
authors.lastname: Schmidt
authors.affiliation: Diabetic Complications Division, Baker IDI Heart & Diabetes Institute, Melbourne, Australia Department of Medicine, Monash University, Melbourne, Australia Karin.jandeleit-dahm@bakeridi.edu.au.
authors.forename: Karin A M
authors.initials: KA
authors.lastname: Jandeleit-Dahm
mesh_terms: D000818:Animals; D001025:Aortitis / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D020022:Genetic Predisposition to Disease; D007111:Immunity, Cellular; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000201:enzymology / Q000276:immunology; D018345:Mice, Knockout; D009247:NADH, NADPH Oxidoreductases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000074624:NADPH Oxidase 1; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D010641:Phenotype; D058226:Plaque, Atherosclerotic; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D012850:Sinus of Valsalva / Q000201:enzymology* / Q000276:immunology / Q000473:pathology
chemical_list: D001057:Apolipoproteins E; D016207:Cytokines; D018836:Inflammation Mediators; D017382:Reactive Oxygen Species; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C000614711:NOX1 protein, mouse; C422943:Nox4 protein, mouse
keywords: NADPH oxidase; atherosclerosis; diabetes; inflammation; oxidative stress