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The Comparison of the Protective Effects of α- and β-Antithrombin against Vascular Endothelial Cell Damage Induced by Histone in Vitro
Antithrombin is a promising option for the treatment of sepsis, and vascular endothelium is an important target for this fatal condition. Here, we aimed to evaluate the protective effects of different glycoforms of antithrombin on histone-induced endothelial cell damage and explore the responsible m...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Georg Thieme Verlag KG
2017
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524836/ https://www.ncbi.nlm.nih.gov/pubmed/31249909 http://dx.doi.org/10.1055/s-0037-1603926 |
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author | Iba, Toshiaki Sasaki, Tetsuya Ohshima, Kazutoshi Sato, Koichi Nagaoka, Isao Thachil, Jecko |
author_facet | Iba, Toshiaki Sasaki, Tetsuya Ohshima, Kazutoshi Sato, Koichi Nagaoka, Isao Thachil, Jecko |
author_sort | Iba, Toshiaki |
collection | PubMed |
description | Antithrombin is a promising option for the treatment of sepsis, and vascular endothelium is an important target for this fatal condition. Here, we aimed to evaluate the protective effects of different glycoforms of antithrombin on histone-induced endothelial cell damage and explore the responsible mechanisms in an experimental model in vitro. Endothelial cells were treated in vitro using histone H4 to induce cellular damage. Various doses of either α- or β-antithrombin were used as treatment interventions, and both cell viability and the levels of lactate dehydrogenase (LDH) in the medium were assessed. Endothelial cell damage was also assessed using microscopic examination and immunofluorescent staining with anti-syndecan-4 and anti-antithrombin antibodies. As a result, both glycoforms of antithrombin significantly improved cell viability when administered at a physiological dose (150 μg/mL). Cellular injury as evaluated using the LDH level was significantly suppressed by β-antithrombin at a supranormal dose (600 μg/mL). Microscopic observation suggested that β-antithrombin suppressed the endothelial cell damage more efficiently than α-antithrombin. β-Antithrombin suppressed the intensity of syndecan-4 staining which became evident after treatment with histone H4, more prominently than α-antithrombin. The distribution of antithrombin was identical to that of syndecan-4. In conclusion, both α- and β-antithrombin can protect vascular endothelial cells from histone H4-induced damage, although the effect was stronger for β-antithrombin. The responsible mechanisms might involve the binding of antithrombin to the glycocalyx on the endothelial surface. These results provide a theoretical basis for the application of antithrombin to the prevention and treatment of sepsis-related endothelial damage. |
format | Online Article Text |
id | pubmed-6524836 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Georg Thieme Verlag KG |
record_format | MEDLINE/PubMed |
spelling | pubmed-65248362019-06-27 The Comparison of the Protective Effects of α- and β-Antithrombin against Vascular Endothelial Cell Damage Induced by Histone in Vitro Iba, Toshiaki Sasaki, Tetsuya Ohshima, Kazutoshi Sato, Koichi Nagaoka, Isao Thachil, Jecko TH Open Antithrombin is a promising option for the treatment of sepsis, and vascular endothelium is an important target for this fatal condition. Here, we aimed to evaluate the protective effects of different glycoforms of antithrombin on histone-induced endothelial cell damage and explore the responsible mechanisms in an experimental model in vitro. Endothelial cells were treated in vitro using histone H4 to induce cellular damage. Various doses of either α- or β-antithrombin were used as treatment interventions, and both cell viability and the levels of lactate dehydrogenase (LDH) in the medium were assessed. Endothelial cell damage was also assessed using microscopic examination and immunofluorescent staining with anti-syndecan-4 and anti-antithrombin antibodies. As a result, both glycoforms of antithrombin significantly improved cell viability when administered at a physiological dose (150 μg/mL). Cellular injury as evaluated using the LDH level was significantly suppressed by β-antithrombin at a supranormal dose (600 μg/mL). Microscopic observation suggested that β-antithrombin suppressed the endothelial cell damage more efficiently than α-antithrombin. β-Antithrombin suppressed the intensity of syndecan-4 staining which became evident after treatment with histone H4, more prominently than α-antithrombin. The distribution of antithrombin was identical to that of syndecan-4. In conclusion, both α- and β-antithrombin can protect vascular endothelial cells from histone H4-induced damage, although the effect was stronger for β-antithrombin. The responsible mechanisms might involve the binding of antithrombin to the glycocalyx on the endothelial surface. These results provide a theoretical basis for the application of antithrombin to the prevention and treatment of sepsis-related endothelial damage. Georg Thieme Verlag KG 2017-06-28 /pmc/articles/PMC6524836/ /pubmed/31249909 http://dx.doi.org/10.1055/s-0037-1603926 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License, which permits unrestricted reproduction and distribution, for non-commercial purposes only; and use and reproduction, but not distribution, of adapted material for non-commercial purposes only, provided the original work is properly cited. |
spellingShingle | Iba, Toshiaki Sasaki, Tetsuya Ohshima, Kazutoshi Sato, Koichi Nagaoka, Isao Thachil, Jecko The Comparison of the Protective Effects of α- and β-Antithrombin against Vascular Endothelial Cell Damage Induced by Histone in Vitro |
title | The Comparison of the Protective Effects of α- and β-Antithrombin against Vascular Endothelial Cell Damage Induced by Histone in Vitro |
title_full | The Comparison of the Protective Effects of α- and β-Antithrombin against Vascular Endothelial Cell Damage Induced by Histone in Vitro |
title_fullStr | The Comparison of the Protective Effects of α- and β-Antithrombin against Vascular Endothelial Cell Damage Induced by Histone in Vitro |
title_full_unstemmed | The Comparison of the Protective Effects of α- and β-Antithrombin against Vascular Endothelial Cell Damage Induced by Histone in Vitro |
title_short | The Comparison of the Protective Effects of α- and β-Antithrombin against Vascular Endothelial Cell Damage Induced by Histone in Vitro |
title_sort | comparison of the protective effects of α- and β-antithrombin against vascular endothelial cell damage induced by histone in vitro |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524836/ https://www.ncbi.nlm.nih.gov/pubmed/31249909 http://dx.doi.org/10.1055/s-0037-1603926 |
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