Sulodexide Prevents Hyperglycemia-Induced Endothelial Dysfunction and Oxidative Stress in Porcine Retinal Arterioles

Sulodexide Prevents Hyperglycemia-Induced Endothelial Dysfunction and Oxidative Stress in Porcine Retinal Arterioles

Diabetes mellitus may cause severe damage to retinal blood vessels. The central aim of this study was to test the hypothesis that sulodexide, a mixture of glycosaminoglycans, has a protective effect against hyperglycemia-induced endothelial dysfunction in the retina. Functional studies were performe...

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Bibliographic Details
Published in:Antioxidants Vol. 12; no. 2; p. 388
Main Authors: Dauth, Alice, Bręborowicz, Andrzej, Ruan, Yue, Tang, Qi, Zadeh, Jenia K, Böhm, Elsa W, Pfeiffer, Norbert, Khedkar, Pratik H, Patzak, Andreas, Vujacic-Mirski, Ksenija, Daiber, Andreas, Gericke, Adrian
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 01-02-2023
MDPI
Subjects:
Animals
Antioxidants
Arterioles
Blood vessels
Diabetes
Diabetes mellitus
Diabetic retinopathy
endothelial dysfunction
Endothelium
Gene expression
Glucose
Glycosaminoglycans
High-performance liquid chromatography
Hyperglycemia
Immunofluorescence
Inflammation
Ischemia
Nitric oxide
NOX4 protein
Oxidants
Oxidative stress
Pathogenesis
Physiological aspects
Reactive oxygen species
Retina
Senescence
sulodexide
Vasodilation
Germany
Netherlands
United States > US
Japan
sulodexide
diabetic retinopathy
endothelial dysfunction
oxidative stress
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Summary:Diabetes mellitus may cause severe damage to retinal blood vessels. The central aim of this study was to test the hypothesis that sulodexide, a mixture of glycosaminoglycans, has a protective effect against hyperglycemia-induced endothelial dysfunction in the retina. 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 (50/5/0.5 μg/mL) or normally concentrated glucose solution (NG, 5.5 mM D-glucose) +/- sulodexide for two hours. Endothelium-dependent and endothelium-independent vasodilatation were measured by videomicroscopy. Reactive oxygen species (ROS) were quantified by dihydroethidium (DHE) fluorescence. Using high-pressure liquid chromatography (HPLC), the intrinsic antioxidant properties of sulodexide were investigated. Quantitative PCR was used to determine mRNA expression of regulatory, inflammatory, and redox genes in retinal arterioles, some of which were subsequently quantified at the protein level by immunofluorescence microscopy. 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 in the vascular wall. Strikingly, sulodexide had a protective effect against hyperglycemia-induced ROS formation in the vascular wall and had a concentration-dependent protective effect against endothelial dysfunction. Although sulodexide itself had only negligible antioxidant properties, it prevented hyperglycemia-induced overexpression of the pro-oxidant redox enzymes, NOX4 and NOX5. The data of the present study provide evidence that sulodexide has a protective effect against hyperglycemia-induced oxidative stress and endothelial dysfunction in porcine retinal arterioles, possibly by modulation of redox enzyme expression.
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ISSN:2076-3921
2076-3921
DOI:10.3390/antiox12020388