Authors:	Dauth, Alice Breborowicz, 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
Title:	Sulodexide prevents hyperglycemia-induced endothelial dysfunction and oxidative stress in porcine retinal arterioles
Online publication date:	26-May-2023
Year of first publication:	2023
Language:	english
Abstract:	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 videomi croscopy. Reactive oxygen species (ROS) were quantified by dihydroethidium (DHE) fluorescence. Using high-pressure liquid chromatography (HPLC), the intrinsic antioxidant properties of sulodex ide 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 oxida tive stress and endothelial dysfunction in porcine retinal arterioles, possibly by modulation of redox enzyme expression.
DDC:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-9121
Version:	Published version
Publication type:	Zeitschriftenaufsatz
Document type specification:	Scientific article
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	Antioxidants 12 2
Pages or article number:	388
Publisher:	MDPI
Publisher place:	Basel
Issue date:	2023
ISSN:	2076-3921
Publisher DOI:	10.3390/antiox12020388
Appears in collections:	DFG-491381577-G