title: Targeted antioxidant therapies in hyperglycemia-mediated endothelial dysfunction.
abstract: Although intensive glycaemic and blood pressure control have reduced the risks of micro- and macrovascular complications, diabetes remains a major cause of cardiovascular events, end-stage renal failure, blindness and neuropathy. It is therefore imperative to understand the underlying mechanisms and to establish effective treatments to prevent, retard or reverse diabetic complications. One area of increased focus is the diabetic vascular endothelium. Hyperglycaemia triggers a cascade of events, not least an increase in reactive oxygen species (ROS) leading to enhanced oxidative stress, with its negative impact on endothelial function. In this review, we explore a unifying hypothesis that increased glucose-mediated ROS leads to endothelial dysfunction as the underpinning causative event triggering accelerated micro- and macrovascular complications. In particular, the consequences of deficiencies in the antioxidant enzyme, glutathione peroxidase, on endothelial dysfunction as a trigger of diabetic micro- and macrovascular complications, will be reviewed. Furthermore, novel antioxidant therapies will be highlighted. Specifically, use of Gpx1-mimetics holds promise as a targeted antioxidant approach and an alternative adjunct therapy to reduce diabetic complications.
authors.affiliation: Oxidative Stress Laboratory, BakerIDI Heart and Diabetes Institute, Melbourne, Australia. judy.dehaan@bakeridi.edu.au
authors.forename: Judy B
authors.initials: JB
authors.lastname: de Haan
authors.forename: Mark E
authors.initials: ME
authors.lastname: Cooper
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D001393:Azoles / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D048909:Diabetes Complications / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000201:enzymology / Q000503:physiopathology*; D005947:Glucose; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000188:drug therapy*; D054833:Isoindoles; D051379:Mice; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016566:Organoselenium Compounds / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1
chemical_list: D000975:Antioxidants; D001057:Apolipoproteins E; D001393:Azoles; D054833:Isoindoles; D051267:NF-E2-Related Factor 2; D016566:Organoselenium Compounds; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C042986:ebselen; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D005947:Glucose; D000094765:Glutathione Peroxidase GPX1