[Current concepts of diabetic atherogenesis].
Morbidity and mortality in patients with diabetes is mainly driven by its vascular manifestations. The underlying pathophysiology of diabetes is centrally linked to increased generation of reactive oxygen species, namely superoxide and hydrogen peroxide. Superoxide, generated upon uncoupling of the mitochondrial respiratory chain, oxidizes endothelial-derived nitric oxide and thus impairs endothelial function. Superoxide-derived hydrogen peroxide is the principal substrate for leukocyte-derived peroxidases, in particular myeloperoxidase, which associates with endothelial cells and has been shown to catalytically oxidize nitric oxide in vivo. Superoxide also promotes synthesis of advanced glycation endproducts, which also exert potent proatherogenic properties. Moreover, superoxide and hydrogen peroxide activate the redox-sensitive transcription factors NF-kappaB and thus mediates expression of proinflammatory proteins like adhesion molecules. Herein some the most recent discoveries in the pathophysiology of diabetic vasculopathy are reviewed.
Baldus
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Universitäres Herzzentrum Hamburg, Klinik und Poliklinik für Kardiologie und Angiologie, Martinistr. 52, 20246 Hamburg. baldus@uke.uni-hamburg.de
Meinertz
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T
D003925:Diabetic Angiopathies / Q000503:physiopathology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
D016328:NF-kappa B; D013481:Superoxides; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D009195:Peroxidase