Sulodexide reduces glucose induced senescence in human retinal endothelial cells

Abstract Chronic exposure of retinal endothelium cells to hyperglycemia is the leading cause of diabetic retinopathy. We evaluated the effect of high glucose concentration on senescence in human retinal endothelial cells (HREC) and modulation of that effect by Sulodexide. Experiments were performed...

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Autores principales:	A. Gericke, K. Suminska-Jasińska, A. Bręborowicz
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/359541a81a264afab2043cce85348718
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spelling	oai:doaj.org-article:359541a81a264afab2043cce853487182021-12-02T15:57:11ZSulodexide reduces glucose induced senescence in human retinal endothelial cells10.1038/s41598-021-90987-w2045-2322https://doaj.org/article/359541a81a264afab2043cce853487182021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90987-whttps://doaj.org/toc/2045-2322Abstract Chronic exposure of retinal endothelium cells to hyperglycemia is the leading cause of diabetic retinopathy. We evaluated the effect of high glucose concentration on senescence in human retinal endothelial cells (HREC) and modulation of that effect by Sulodexide. Experiments were performed on HREC undergoing in vitro replicative senescence in standard medium or medium supplemented with glucose 20 mmol/L (GLU) or mannitol 20 mnol/L (MAN). Effect of Sulodexide 0.5 LRU/mL (SUL) on the process of HREC senescence was studied. Glucose 20 mmol/L accelerates senescence of HREC: population doubling time (+ 58%, p < 0.001) β-galactosidase activity (+ 60%, p < 0.002) intracellular oxidative stress (+ 65%, p < 0.01), expression of p53 gene (+ 118%, p < 0.001). Senescent HREC had also reduced transendothelial electrical resistance (TEER) (− 30%, p < 0.001). Mannitol 20 mmol/L used in the same scenario as glucose did not induce HREC senescence. In HREC exposed to GLU and SUL, the senescent changes were smaller. HREC, which became senescent in the presence of GLU, demonstrated higher expression of genes regulating the synthesis of Il6 and VEGF-A, which was reflected by increased secretion of these cytokines (IL6 + 125%, p < 0.001 vs control and VEGF-A + 124% p < 0.001 vs control). These effects were smaller in the presence of SUL, and additionally, an increase of TEER in the senescent HREC was observed. Chronic exposure of HREC to high glucose concentration in medium accelerates their senescence, and that process is reduced when the cells are simultaneously exposed to Sulodexide. Additionally, Sulodexide decreases the secretion of IL6 and VEGF-A from senescent HREC and increases their TEER.A. GerickeK. Suminska-JasińskaA. BręborowiczNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q A. Gericke K. Suminska-Jasińska A. Bręborowicz Sulodexide reduces glucose induced senescence in human retinal endothelial cells
description	Abstract Chronic exposure of retinal endothelium cells to hyperglycemia is the leading cause of diabetic retinopathy. We evaluated the effect of high glucose concentration on senescence in human retinal endothelial cells (HREC) and modulation of that effect by Sulodexide. Experiments were performed on HREC undergoing in vitro replicative senescence in standard medium or medium supplemented with glucose 20 mmol/L (GLU) or mannitol 20 mnol/L (MAN). Effect of Sulodexide 0.5 LRU/mL (SUL) on the process of HREC senescence was studied. Glucose 20 mmol/L accelerates senescence of HREC: population doubling time (+ 58%, p < 0.001) β-galactosidase activity (+ 60%, p < 0.002) intracellular oxidative stress (+ 65%, p < 0.01), expression of p53 gene (+ 118%, p < 0.001). Senescent HREC had also reduced transendothelial electrical resistance (TEER) (− 30%, p < 0.001). Mannitol 20 mmol/L used in the same scenario as glucose did not induce HREC senescence. In HREC exposed to GLU and SUL, the senescent changes were smaller. HREC, which became senescent in the presence of GLU, demonstrated higher expression of genes regulating the synthesis of Il6 and VEGF-A, which was reflected by increased secretion of these cytokines (IL6 + 125%, p < 0.001 vs control and VEGF-A + 124% p < 0.001 vs control). These effects were smaller in the presence of SUL, and additionally, an increase of TEER in the senescent HREC was observed. Chronic exposure of HREC to high glucose concentration in medium accelerates their senescence, and that process is reduced when the cells are simultaneously exposed to Sulodexide. Additionally, Sulodexide decreases the secretion of IL6 and VEGF-A from senescent HREC and increases their TEER.
format	article
author	A. Gericke K. Suminska-Jasińska A. Bręborowicz
author_facet	A. Gericke K. Suminska-Jasińska A. Bręborowicz
author_sort	A. Gericke
title	Sulodexide reduces glucose induced senescence in human retinal endothelial cells
title_short	Sulodexide reduces glucose induced senescence in human retinal endothelial cells
title_full	Sulodexide reduces glucose induced senescence in human retinal endothelial cells
title_fullStr	Sulodexide reduces glucose induced senescence in human retinal endothelial cells
title_full_unstemmed	Sulodexide reduces glucose induced senescence in human retinal endothelial cells
title_sort	sulodexide reduces glucose induced senescence in human retinal endothelial cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/359541a81a264afab2043cce85348718
work_keys_str_mv	AT agericke sulodexidereducesglucoseinducedsenescenceinhumanretinalendothelialcells AT ksuminskajasinska sulodexidereducesglucoseinducedsenescenceinhumanretinalendothelialcells AT abreborowicz sulodexidereducesglucoseinducedsenescenceinhumanretinalendothelialcells
_version_	1718385321370976256

Sulodexide reduces glucose induced senescence in human retinal endothelial cells

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