Summary
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-κB and thus mediates expression of proinflammatory proteins like adhesion molecules. Herein some the most recent discoveries in the pathophysiology of diabetic vasculopathy are reviewed.
Zusammenfassung
Die vaskulären Manifestationen des Diabetes mellitus sind prognostisch entscheidend für dessen hohe Morbidität und Mortalität. Für die zugrunde liegende Pathophysiologie erscheint die Generation reaktiver Sauerstoffspezies, allen voran Superoxidanionen und Wasserstoffperoxid, von zentraler Bedeutung. Superoxidanionen, gebildet durch die Entkoppelung der mitochondrialen Atmungskette, oxidieren endothelial generiertes Stickstoffmonoxid und verschlechtern so die Endothelfunktion. Superoxidanionen dismutieren spontan oder katalytisch zu Wasserstoffperoxid, dem Substrat des leukozytären Hämproteins Myeloperoxidase, welches endothelial akkumuliert und NO in vivo oxidiert. Superoxidanionen fördern auch die Synthese fortgeschrittener Glykosilierungsprodukte, die ihrerseits wiederum vielseitige proatherogene Eigenschaften aufweisen. Schließlich aktivieren Superoxidanionen sowie Wasserstoffperoxid redoxsensitive Transkriptionsfaktoren wie NF-κB und regulieren so die Expression proinflammatorischer Proteine wie endothelialer Adhäsionsmoleküle. In dieser Arbeit werden einige der wichtigsten aktuellen pathophysiologischen Konzepte der diabetischen Vaskulopathie diskutiert.
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Baldus, S., Meinertz, T. Aktuelle Konzepte der diabetischen Atherogenese. Clin Res Cardiol 95 (Suppl 1), i1–i6 (2006). https://doi.org/10.1007/s00392-006-1114-z
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DOI: https://doi.org/10.1007/s00392-006-1114-z