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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MDPI AG
2023-02-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/2/388 |
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| author | Alice Dauth Andrzej Bręborowicz Yue Ruan Qi Tang Jenia K. Zadeh Elsa W. Böhm Norbert Pfeiffer Pratik H. Khedkar Andreas Patzak Ksenija Vujacic-Mirski Andreas Daiber Adrian Gericke |
| author_facet | Alice Dauth Andrzej Bręborowicz Yue Ruan Qi Tang Jenia K. Zadeh Elsa W. Böhm Norbert Pfeiffer Pratik H. Khedkar Andreas Patzak Ksenija Vujacic-Mirski Andreas Daiber Adrian Gericke |
| author_sort | Alice Dauth |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T09:14:22Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-11T09:14:22Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-c947c6c921884d968c6403c5e420ce412023-11-16T18:47:29ZengMDPI AGAntioxidants2076-39212023-02-0112238810.3390/antiox12020388Sulodexide Prevents Hyperglycemia-Induced Endothelial Dysfunction and Oxidative Stress in Porcine Retinal ArteriolesAlice Dauth0Andrzej Bręborowicz1Yue Ruan2Qi Tang3Jenia K. Zadeh4Elsa W. Böhm5Norbert Pfeiffer6Pratik H. Khedkar7Andreas Patzak8Ksenija Vujacic-Mirski9Andreas Daiber10Adrian Gericke11Department of Neurosurgery, University Medical Center, Johannes Gutenberg University, Langenbeckstr. 1, 55131 Mainz, GermanyDepartment of Pathophysiology, Poznań University of Medical Sciences, 60-512 Poznań, PolandDepartment of Ophthalmology, University Medical Center, Johannes Gutenberg University, Langenbeckstr. 1, 55131 Mainz, GermanyDepartment of Ophthalmology, University Medical Center, Johannes Gutenberg University, Langenbeckstr. 1, 55131 Mainz, GermanyDepartment of Ophthalmology, University Medical Center, Johannes Gutenberg University, Langenbeckstr. 1, 55131 Mainz, GermanyDepartment of Ophthalmology, University Medical Center, Johannes Gutenberg University, Langenbeckstr. 1, 55131 Mainz, GermanyDepartment of Ophthalmology, University Medical Center, Johannes Gutenberg University, Langenbeckstr. 1, 55131 Mainz, GermanyInstitute of Translational Physiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, GermanyInstitute of Translational Physiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, GermanyDepartment of Cardiology, Cardiology 1, University Medical Center, Johannes Gutenberg University, Langenbeckstr. 1, 55131 Mainz, GermanyDepartment of Cardiology, Cardiology 1, University Medical Center, Johannes Gutenberg University, Langenbeckstr. 1, 55131 Mainz, GermanyDepartment of Ophthalmology, University Medical Center, Johannes Gutenberg University, Langenbeckstr. 1, 55131 Mainz, GermanyDiabetes 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.https://www.mdpi.com/2076-3921/12/2/388diabetic retinopathyendothelial dysfunctionoxidative stresssulodexide |
| spellingShingle | Alice Dauth Andrzej Bręborowicz Yue Ruan Qi Tang Jenia K. Zadeh Elsa W. Böhm Norbert Pfeiffer Pratik H. Khedkar Andreas Patzak Ksenija Vujacic-Mirski Andreas Daiber Adrian Gericke Sulodexide Prevents Hyperglycemia-Induced Endothelial Dysfunction and Oxidative Stress in Porcine Retinal Arterioles Antioxidants diabetic retinopathy endothelial dysfunction oxidative stress sulodexide |
| title | Sulodexide Prevents Hyperglycemia-Induced Endothelial Dysfunction and Oxidative Stress in Porcine Retinal Arterioles |
| title_full | Sulodexide Prevents Hyperglycemia-Induced Endothelial Dysfunction and Oxidative Stress in Porcine Retinal Arterioles |
| title_fullStr | Sulodexide Prevents Hyperglycemia-Induced Endothelial Dysfunction and Oxidative Stress in Porcine Retinal Arterioles |
| title_full_unstemmed | Sulodexide Prevents Hyperglycemia-Induced Endothelial Dysfunction and Oxidative Stress in Porcine Retinal Arterioles |
| title_short | Sulodexide Prevents Hyperglycemia-Induced Endothelial Dysfunction and Oxidative Stress in Porcine Retinal Arterioles |
| title_sort | sulodexide prevents hyperglycemia induced endothelial dysfunction and oxidative stress in porcine retinal arterioles |
| topic | diabetic retinopathy endothelial dysfunction oxidative stress sulodexide |
| url | https://www.mdpi.com/2076-3921/12/2/388 |
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