Einfluss von Sulodexid auf die Endothelfunktion retinaler Arteriolen im Hyperglykämiemodell
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Abstract
Purpose: Diabetes mellitus may cause severe damage to the retinal vascular endothelium .The central aim of this study was to test the hypothesis that sulodexide, a highly purified mixture of glycosaminoglycans, protects from hyperglycemia-induced endothelial dysfunction in the retina.
Methods:Functional studies were performed in isolated porcine retinal arterioles. Vessels were cannulated and incubated with highly concentrated glucose solution (HG, 25 mM D-glucose) +/- sulodexide (50/5/0.5μg/ml) versus normally concentrated glucose solution (NG, 5.5 mM D-glucose) +/- sulodexide for two hours. Next, endothelium-dependent and endothelium-independent vasodilatation to bradykinin and nitroprusside, respectively, was evaluated by videomicroscopy. Reactive oxygen species (ROS) were quantified by DHE-staining. Real-time PCR was used to determine mRNA expression of prooxidant (NOX2, NOX4, NOX5) redox genes, which were subsequently quantified at protein level by immunofluorescence microscopy.
Results:We found that incubation of retinal arterioles with HG caused significant impairment of endothelium-dependent vasodilation whereas endothelium-independent responses were not affected. In the HG group, ROS formation was markedly increased, indicative of oxidative stress. Strikingly, sulodexide concentration-dependently protected from hyperglycemia- induced endothelial dysfunction and ROS formation. Furthermore, sulodexide decreased expression of the prooxidant redox enzymes, NOX4 and NOX5.
Conclusion:Sulodexide protects from hyperglycemia-induced oxidative stress and endothelial dysfunction in porcine retinal arterioles by modulation of redox enzyme expression. From a clinical point of view, sulodexide might become beneficial for the treatment of diabetic retinopathy.