Linking RAGE and Nox in diabetic micro- and macrovascular complications.
Diabetes-associated micro- and macrovascular complications contribute to the increased morbidity and mortality observed in diabetes. Diabetes leads to accelerated generation of advanced glycation end products (AGEs) and activation of their receptor, RAGE, as well as activation of NAD(P)H oxidase (Nox), an enzyme dedicated to the production of reactive oxygen species, which ultimately leads to a pro-inflammatory environment characterised by oxidative stress. This review outlines the current evidence about the contribution of and interaction between the AGE-RAGE axis and Nox derived ROS formation in the development and progression of micro- and macrovascular diabetic complications (especially in atherosclerosis and nephropathy), and the mechanisms by which this occurs. We also outline novel treatments targeting the AGE-RAGE axis and specific Nox isoforms, which hold great promise in attenuating the development of diabetes-associated atherosclerosis and diabetic nephropathy.
Diabetic Complications Division, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia; Central Clinical School, Department of Medicine, Monash University, Melbourne, Australia.
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Koulis
Diabetic Complications Division, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia; Central Clinical School, Department of Medicine, Monash University, Melbourne, Australia.
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Watson
Diabetic Complications Division, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia; Central Clinical School, Department of Medicine, Monash University, Melbourne, Australia.
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Gray
Diabetic Complications Division, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia; Central Clinical School, Department of Medicine, Monash University, Melbourne, Australia. Electronic address: karin.jandeleit-dahm@bakeridi.edu.au.
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Jandeleit-Dahm
D000818:Animals; D050197:Atherosclerosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000235:genetics* / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000235:genetics / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism / Q000502:physiology; D006801:Humans; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000009:adverse effects / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products / Q000502:physiology*
C000593871:AGER protein, human; D017127:Glycation End Products, Advanced; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases; C402799:NOX1 protein, human
Atherosclerosis; Diabetes mellitus; Glycation; NADPH oxidases; Nephropathy; Oxidative stress; RAGE; Vascular complications