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Association Between Nitric Oxide, Oxidative Stress, Eryptosis, Red Blood Cell Microparticles, and Vascular Function in Sickle Cell Anemia
Chronic hemolysis, enhanced oxidative stress, and decreased nitric oxide (NO) bioavailability promote vasculopathy in sickle cell anemia (SCA). Oxidative stress and NO are known to modulate eryptosis in healthy red blood cells (RBCs); however, their role in SCA eryptosis and their impact on the gene...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672038/ https://www.ncbi.nlm.nih.gov/pubmed/33250889 http://dx.doi.org/10.3389/fimmu.2020.551441 |
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author | Nader, Elie Romana, Marc Guillot, Nicolas Fort, Romain Stauffer, Emeric Lemonne, Nathalie Garnier, Yohann Skinner, Sarah Chambers Etienne-Julan, Maryse Robert, Mélanie Gauthier, Alexandra Cannas, Giovanna Antoine-Jonville, Sophie Tressières, Benoît Hardy-Dessources, Marie-Dominique Bertrand, Yves Martin, Cyril Renoux, Céline Joly, Philippe Grau, Marijke Connes, Philippe |
author_facet | Nader, Elie Romana, Marc Guillot, Nicolas Fort, Romain Stauffer, Emeric Lemonne, Nathalie Garnier, Yohann Skinner, Sarah Chambers Etienne-Julan, Maryse Robert, Mélanie Gauthier, Alexandra Cannas, Giovanna Antoine-Jonville, Sophie Tressières, Benoît Hardy-Dessources, Marie-Dominique Bertrand, Yves Martin, Cyril Renoux, Céline Joly, Philippe Grau, Marijke Connes, Philippe |
author_sort | Nader, Elie |
collection | PubMed |
description | Chronic hemolysis, enhanced oxidative stress, and decreased nitric oxide (NO) bioavailability promote vasculopathy in sickle cell anemia (SCA). Oxidative stress and NO are known to modulate eryptosis in healthy red blood cells (RBCs); however, their role in SCA eryptosis and their impact on the genesis of RBC-derived microparticles (RBC-MPs) remains poorly described. RBC-MPs could play a role in vascular dysfunction in SCA. The aims of this study were to evaluate the roles of oxidative stress and NO in eryptosis and RBC-MPs release, and to determine whether RBC-MPs could be involved in vascular dysfunction in SCA. Markers of eryptosis and oxidative stress, plasma RBC-MPs concentration and arterial stiffness were compared between SCA and healthy (AA) individuals. In-vitro experiments were performed to test: 1) the effects of oxidative stress (antioxidant: n-acetylcysteine (NAC); pro-oxidant: cumene hydroperoxide) and NO (NO donor: sodium nitroprusside (SNP); NO-synthase inhibitor (L-NIO)) on eryptosis, RBC deformability and RBC-MP genesis; 2) the effects of SCA/AA-RBC-MPs on human aortic endothelial cell (HAEC) inflammatory phenotype and TLR4 pathway. Eryptosis, RBC-MPs, oxidative stress and arterial stiffness were increased in SCA. NAC increased RBC deformability and decreased eryptosis and RBC-MPs release, while cumene did the opposite. SNP increased RBC deformability and limited eryptosis, but had no effect on RBC-MPs. L-NIO did not affect these parameters. Arterial stiffness was correlated with RBC-MPs concentration in SCA. RBC-MPs isolated directly from SCA blood increased adhesion molecules expression and the production of cytokines by HAEC compared to those isolated from AA blood. TLR4 inhibition alleviated these effects. Our data show that oxidative stress could promote eryptosis and the release of RBC-MPs that are potentially involved in macrovascular dysfunction in SCA. |
format | Online Article Text |
id | pubmed-7672038 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-76720382020-11-26 Association Between Nitric Oxide, Oxidative Stress, Eryptosis, Red Blood Cell Microparticles, and Vascular Function in Sickle Cell Anemia Nader, Elie Romana, Marc Guillot, Nicolas Fort, Romain Stauffer, Emeric Lemonne, Nathalie Garnier, Yohann Skinner, Sarah Chambers Etienne-Julan, Maryse Robert, Mélanie Gauthier, Alexandra Cannas, Giovanna Antoine-Jonville, Sophie Tressières, Benoît Hardy-Dessources, Marie-Dominique Bertrand, Yves Martin, Cyril Renoux, Céline Joly, Philippe Grau, Marijke Connes, Philippe Front Immunol Immunology Chronic hemolysis, enhanced oxidative stress, and decreased nitric oxide (NO) bioavailability promote vasculopathy in sickle cell anemia (SCA). Oxidative stress and NO are known to modulate eryptosis in healthy red blood cells (RBCs); however, their role in SCA eryptosis and their impact on the genesis of RBC-derived microparticles (RBC-MPs) remains poorly described. RBC-MPs could play a role in vascular dysfunction in SCA. The aims of this study were to evaluate the roles of oxidative stress and NO in eryptosis and RBC-MPs release, and to determine whether RBC-MPs could be involved in vascular dysfunction in SCA. Markers of eryptosis and oxidative stress, plasma RBC-MPs concentration and arterial stiffness were compared between SCA and healthy (AA) individuals. In-vitro experiments were performed to test: 1) the effects of oxidative stress (antioxidant: n-acetylcysteine (NAC); pro-oxidant: cumene hydroperoxide) and NO (NO donor: sodium nitroprusside (SNP); NO-synthase inhibitor (L-NIO)) on eryptosis, RBC deformability and RBC-MP genesis; 2) the effects of SCA/AA-RBC-MPs on human aortic endothelial cell (HAEC) inflammatory phenotype and TLR4 pathway. Eryptosis, RBC-MPs, oxidative stress and arterial stiffness were increased in SCA. NAC increased RBC deformability and decreased eryptosis and RBC-MPs release, while cumene did the opposite. SNP increased RBC deformability and limited eryptosis, but had no effect on RBC-MPs. L-NIO did not affect these parameters. Arterial stiffness was correlated with RBC-MPs concentration in SCA. RBC-MPs isolated directly from SCA blood increased adhesion molecules expression and the production of cytokines by HAEC compared to those isolated from AA blood. TLR4 inhibition alleviated these effects. Our data show that oxidative stress could promote eryptosis and the release of RBC-MPs that are potentially involved in macrovascular dysfunction in SCA. Frontiers Media S.A. 2020-11-04 /pmc/articles/PMC7672038/ /pubmed/33250889 http://dx.doi.org/10.3389/fimmu.2020.551441 Text en Copyright © 2020 Nader, Romana, Guillot, Fort, Stauffer, Lemonne, Garnier, Skinner, Etienne-Julan, Robert, Gauthier, Cannas, Antoine-Jonville, Tressières, Hardy-Dessources, Bertrand, Martin, Renoux, Joly, Grau and Connes http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Nader, Elie Romana, Marc Guillot, Nicolas Fort, Romain Stauffer, Emeric Lemonne, Nathalie Garnier, Yohann Skinner, Sarah Chambers Etienne-Julan, Maryse Robert, Mélanie Gauthier, Alexandra Cannas, Giovanna Antoine-Jonville, Sophie Tressières, Benoît Hardy-Dessources, Marie-Dominique Bertrand, Yves Martin, Cyril Renoux, Céline Joly, Philippe Grau, Marijke Connes, Philippe Association Between Nitric Oxide, Oxidative Stress, Eryptosis, Red Blood Cell Microparticles, and Vascular Function in Sickle Cell Anemia |
title | Association Between Nitric Oxide, Oxidative Stress, Eryptosis, Red Blood Cell Microparticles, and Vascular Function in Sickle Cell Anemia |
title_full | Association Between Nitric Oxide, Oxidative Stress, Eryptosis, Red Blood Cell Microparticles, and Vascular Function in Sickle Cell Anemia |
title_fullStr | Association Between Nitric Oxide, Oxidative Stress, Eryptosis, Red Blood Cell Microparticles, and Vascular Function in Sickle Cell Anemia |
title_full_unstemmed | Association Between Nitric Oxide, Oxidative Stress, Eryptosis, Red Blood Cell Microparticles, and Vascular Function in Sickle Cell Anemia |
title_short | Association Between Nitric Oxide, Oxidative Stress, Eryptosis, Red Blood Cell Microparticles, and Vascular Function in Sickle Cell Anemia |
title_sort | association between nitric oxide, oxidative stress, eryptosis, red blood cell microparticles, and vascular function in sickle cell anemia |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672038/ https://www.ncbi.nlm.nih.gov/pubmed/33250889 http://dx.doi.org/10.3389/fimmu.2020.551441 |
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