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...
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.551441/full |
| _version_ | 1818116112699621376 |
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| author | Elie Nader Elie Nader Marc Romana Marc Romana Marc Romana Nicolas Guillot Romain Fort Romain Fort Romain Fort Emeric Stauffer Emeric Stauffer Emeric Stauffer Nathalie Lemonne Yohann Garnier Yohann Garnier Yohann Garnier Sarah Chambers Skinner Sarah Chambers Skinner Maryse Etienne-Julan Mélanie Robert Alexandra Gauthier Alexandra Gauthier Giovanna Cannas Giovanna Cannas Sophie Antoine-Jonville Benoît Tressières Marie-Dominique Hardy-Dessources Marie-Dominique Hardy-Dessources Marie-Dominique Hardy-Dessources Yves Bertrand Cyril Martin Cyril Martin Céline Renoux Céline Renoux Céline Renoux Philippe Joly Philippe Joly Philippe Joly Marijke Grau Philippe Connes Philippe Connes Philippe Connes |
| author_facet | Elie Nader Elie Nader Marc Romana Marc Romana Marc Romana Nicolas Guillot Romain Fort Romain Fort Romain Fort Emeric Stauffer Emeric Stauffer Emeric Stauffer Nathalie Lemonne Yohann Garnier Yohann Garnier Yohann Garnier Sarah Chambers Skinner Sarah Chambers Skinner Maryse Etienne-Julan Mélanie Robert Alexandra Gauthier Alexandra Gauthier Giovanna Cannas Giovanna Cannas Sophie Antoine-Jonville Benoît Tressières Marie-Dominique Hardy-Dessources Marie-Dominique Hardy-Dessources Marie-Dominique Hardy-Dessources Yves Bertrand Cyril Martin Cyril Martin Céline Renoux Céline Renoux Céline Renoux Philippe Joly Philippe Joly Philippe Joly Marijke Grau Philippe Connes Philippe Connes Philippe Connes |
| author_sort | Elie Nader |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-11T04:17:20Z |
| format | Article |
| id | doaj.art-327d7cbdbea248aeb284d431ff770a87 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T04:17:20Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-327d7cbdbea248aeb284d431ff770a872022-12-22T01:21:12ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-11-011110.3389/fimmu.2020.551441551441Association Between Nitric Oxide, Oxidative Stress, Eryptosis, Red Blood Cell Microparticles, and Vascular Function in Sickle Cell AnemiaElie Nader0Elie Nader1Marc Romana2Marc Romana3Marc Romana4Nicolas Guillot5Romain Fort6Romain Fort7Romain Fort8Emeric Stauffer9Emeric Stauffer10Emeric Stauffer11Nathalie Lemonne12Yohann Garnier13Yohann Garnier14Yohann Garnier15Sarah Chambers Skinner16Sarah Chambers Skinner17Maryse Etienne-Julan18Mélanie Robert19Alexandra Gauthier20Alexandra Gauthier21Giovanna Cannas22Giovanna Cannas23Sophie Antoine-Jonville24Benoît Tressières25Marie-Dominique Hardy-Dessources26Marie-Dominique Hardy-Dessources27Marie-Dominique Hardy-Dessources28Yves Bertrand29Cyril Martin30Cyril Martin31Céline Renoux32Céline Renoux33Céline Renoux34Philippe Joly35Philippe Joly36Philippe Joly37Marijke Grau38Philippe Connes39Philippe Connes40Philippe Connes41Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team « Vascular Biology and Red Blood Cell », Université Claude Bernard Lyon 1, Université de Lyon, Lyon, FranceLaboratoire d’Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, FranceLaboratoire d’Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, FranceUniversité des Antilles, Pointe-à-Pitre, FranceUniversité de Paris, Paris, FranceLaboratoire Carmen Inserm, Université Claude Bernard Lyon 1, Université de Lyon, Villeurbanne, FranceLaboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team « Vascular Biology and Red Blood Cell », Université Claude Bernard Lyon 1, Université de Lyon, Lyon, FranceLaboratoire d’Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, FranceDépartement de Médecine Interne, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, FranceLaboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team « Vascular Biology and Red Blood Cell », Université Claude Bernard Lyon 1, Université de Lyon, Lyon, FranceLaboratoire d’Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, FranceCentre de Médecine du Sommeil et des Maladies Respiratoires, Hospices Civils de Lyon, Hôpital de la Croix Rousse, Lyon, FranceUnité Transversale de la Drépanocytose, Hôpital de Pointe-á-Pitre, Hôpital Ricou, Guadeloupe, FranceLaboratoire d’Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, FranceUniversité des Antilles, Pointe-à-Pitre, FranceUniversité de Paris, Paris, FranceLaboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team « Vascular Biology and Red Blood Cell », Université Claude Bernard Lyon 1, Université de Lyon, Lyon, FranceLaboratoire d’Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, FranceUnité Transversale de la Drépanocytose, Hôpital de Pointe-á-Pitre, Hôpital Ricou, Guadeloupe, FranceErytech Pharma, Lyon, FranceLaboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team « Vascular Biology and Red Blood Cell », Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France0Institut d’Hématologie et d’Oncologie Pédiatrique, Hospices Civils de Lyon, Lyon, FranceLaboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team « Vascular Biology and Red Blood Cell », Université Claude Bernard Lyon 1, Université de Lyon, Lyon, FranceDépartement de Médecine Interne, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, FranceUniversité des Antilles, Pointe-à-Pitre, France1Centre Investigation Clinique Antilles Guyane, 1424 Inserm, Academic Hospital of Pointe-á-Pitre, Pointe-á-Pitre, Guadeloupe, FranceLaboratoire d’Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, FranceUniversité des Antilles, Pointe-à-Pitre, FranceUniversité de Paris, Paris, France0Institut d’Hématologie et d’Oncologie Pédiatrique, Hospices Civils de Lyon, Lyon, FranceLaboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team « Vascular Biology and Red Blood Cell », Université Claude Bernard Lyon 1, Université de Lyon, Lyon, FranceLaboratoire d’Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, FranceLaboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team « Vascular Biology and Red Blood Cell », Université Claude Bernard Lyon 1, Université de Lyon, Lyon, FranceLaboratoire d’Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France2Laboratoire de Biochimie et de Biologie Moléculaire, UF de Biochimie des Pathologies érythrocytaires, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, Lyon, FranceLaboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team « Vascular Biology and Red Blood Cell », Université Claude Bernard Lyon 1, Université de Lyon, Lyon, FranceLaboratoire d’Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France2Laboratoire de Biochimie et de Biologie Moléculaire, UF de Biochimie des Pathologies érythrocytaires, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, Lyon, France3Molecular and Cellular Sport Medicine, Deutsche Sporthochschule Köln, Köln, GermanyLaboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team « Vascular Biology and Red Blood Cell », Université Claude Bernard Lyon 1, Université de Lyon, Lyon, FranceLaboratoire d’Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France4Institut Universitaire de France, Paris, FranceChronic 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.https://www.frontiersin.org/articles/10.3389/fimmu.2020.551441/fullsickle cell anemiaeryptosisred blood cell microparticlesvascular dysfunctionendothelial cellsTLR4 |
| spellingShingle | Elie Nader Elie Nader Marc Romana Marc Romana Marc Romana Nicolas Guillot Romain Fort Romain Fort Romain Fort Emeric Stauffer Emeric Stauffer Emeric Stauffer Nathalie Lemonne Yohann Garnier Yohann Garnier Yohann Garnier Sarah Chambers Skinner Sarah Chambers Skinner Maryse Etienne-Julan Mélanie Robert Alexandra Gauthier Alexandra Gauthier Giovanna Cannas Giovanna Cannas Sophie Antoine-Jonville Benoît Tressières Marie-Dominique Hardy-Dessources Marie-Dominique Hardy-Dessources Marie-Dominique Hardy-Dessources Yves Bertrand Cyril Martin Cyril Martin Céline Renoux Céline Renoux Céline Renoux Philippe Joly Philippe Joly Philippe Joly Marijke Grau Philippe Connes Philippe Connes Philippe Connes Association Between Nitric Oxide, Oxidative Stress, Eryptosis, Red Blood Cell Microparticles, and Vascular Function in Sickle Cell Anemia Frontiers in Immunology sickle cell anemia eryptosis red blood cell microparticles vascular dysfunction endothelial cells TLR4 |
| 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 | sickle cell anemia eryptosis red blood cell microparticles vascular dysfunction endothelial cells TLR4 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.551441/full |
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