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Association Between Nitric Oxide, Oxidative Stress, Eryptosis, Red Blood Cell Microparticles, and Vascular Function in Sickle Cell Anemia.
Front Immunol. 2020; 11:551441.FI

Abstract

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.

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Authors+Show Affiliations

Nader E
Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team « Vascular Biology and Red Blood Cell », Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France. Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France.
Romana M
Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France. Université des Antilles, Pointe-à-Pitre, France. Université de Paris, Paris, France.
Guillot N
Laboratoire Carmen Inserm, Université Claude Bernard Lyon 1, Université de Lyon, Villeurbanne, France.
Fort R
Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team « Vascular Biology and Red Blood Cell », Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France. Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France. Département de Médecine Interne, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
Stauffer E
Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team « Vascular Biology and Red Blood Cell », Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France. Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France. Centre de Médecine du Sommeil et des Maladies Respiratoires, Hospices Civils de Lyon, Hôpital de la Croix Rousse, Lyon, France.
Lemonne N
Unité Transversale de la Drépanocytose, Hôpital de Pointe-á-Pitre, Hôpital Ricou, Guadeloupe, France.
Garnier Y
Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France. Université des Antilles, Pointe-à-Pitre, France. Université de Paris, Paris, France.
Skinner SC
Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team « Vascular Biology and Red Blood Cell », Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France. Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France.
Etienne-Julan M
Unité Transversale de la Drépanocytose, Hôpital de Pointe-á-Pitre, Hôpital Ricou, Guadeloupe, France.
Robert M
Erytech Pharma, Lyon, France.
Gauthier A
Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team « Vascular Biology and Red Blood Cell », Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France. Institut d'Hématologie et d'Oncologie Pédiatrique, Hospices Civils de Lyon, Lyon, France.
Cannas G
Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team « Vascular Biology and Red Blood Cell », Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France. Département de Médecine Interne, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
Antoine-Jonville S
Université des Antilles, Pointe-à-Pitre, France.
Tressières B
Centre Investigation Clinique Antilles Guyane, 1424 Inserm, Academic Hospital of Pointe-á-Pitre, Pointe-á-Pitre, Guadeloupe, France.
Hardy-Dessources MD
Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France. Université des Antilles, Pointe-à-Pitre, France. Université de Paris, Paris, France.
Bertrand Y
Institut d'Hématologie et d'Oncologie Pédiatrique, Hospices Civils de Lyon, Lyon, France.
Martin C
Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team « Vascular Biology and Red Blood Cell », Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France. Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France.
Renoux C
Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team « Vascular Biology and Red Blood Cell », Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France. Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France. Laboratoire de Biochimie et de Biologie Moléculaire, UF de Biochimie des Pathologies érythrocytaires, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, Lyon, France.
Joly P
Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team « Vascular Biology and Red Blood Cell », Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France. Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France. Laboratoire de Biochimie et de Biologie Moléculaire, UF de Biochimie des Pathologies érythrocytaires, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, Lyon, France.
Grau M
Molecular and Cellular Sport Medicine, Deutsche Sporthochschule Köln, Köln, Germany.
Connes P
Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team « Vascular Biology and Red Blood Cell », Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France. Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France. Institut Universitaire de France, Paris, France.

MeSH

AdolescentAdultAnemia, Sickle CellCell-Derived MicroparticlesChildChild, PreschoolEryptosisErythrocytes, AbnormalFemaleHumansMaleNitric OxideOxidative StressVascular Stiffness

Pub Type(s)

Clinical Trial
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33250889

Citation

Nader, Elie, et al. "Association Between Nitric Oxide, Oxidative Stress, Eryptosis, Red Blood Cell Microparticles, and Vascular Function in Sickle Cell Anemia." Frontiers in Immunology, vol. 11, 2020, p. 551441.
Nader E, Romana M, Guillot N, et al. Association Between Nitric Oxide, Oxidative Stress, Eryptosis, Red Blood Cell Microparticles, and Vascular Function in Sickle Cell Anemia. Front Immunol. 2020;11:551441.
Nader, E., Romana, M., Guillot, N., Fort, R., Stauffer, E., Lemonne, N., Garnier, Y., Skinner, S. C., Etienne-Julan, M., Robert, M., Gauthier, A., Cannas, G., Antoine-Jonville, S., Tressières, B., Hardy-Dessources, M. D., Bertrand, Y., Martin, C., Renoux, C., Joly, P., ... Connes, P. (2020). Association Between Nitric Oxide, Oxidative Stress, Eryptosis, Red Blood Cell Microparticles, and Vascular Function in Sickle Cell Anemia. Frontiers in Immunology, 11, 551441. https://doi.org/10.3389/fimmu.2020.551441
Nader E, et al. Association Between Nitric Oxide, Oxidative Stress, Eryptosis, Red Blood Cell Microparticles, and Vascular Function in Sickle Cell Anemia. Front Immunol. 2020;11:551441. PubMed PMID: 33250889.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association Between Nitric Oxide, Oxidative Stress, Eryptosis, Red Blood Cell Microparticles, and Vascular Function in Sickle Cell Anemia. AU - Nader,Elie, AU - Romana,Marc, AU - Guillot,Nicolas, AU - Fort,Romain, AU - Stauffer,Emeric, AU - Lemonne,Nathalie, AU - Garnier,Yohann, AU - Skinner,Sarah Chambers, AU - Etienne-Julan,Maryse, AU - Robert,Mélanie, AU - Gauthier,Alexandra, AU - Cannas,Giovanna, AU - Antoine-Jonville,Sophie, AU - Tressières,Benoît, AU - Hardy-Dessources,Marie-Dominique, AU - Bertrand,Yves, AU - Martin,Cyril, AU - Renoux,Céline, AU - Joly,Philippe, AU - Grau,Marijke, AU - Connes,Philippe, Y1 - 2020/11/04/ PY - 2020/04/13/received PY - 2020/10/14/accepted PY - 2020/11/30/entrez PY - 2020/12/1/pubmed PY - 2021/5/1/medline KW - TLR4 KW - endothelial cells KW - eryptosis KW - red blood cell microparticles KW - sickle cell anemia KW - vascular dysfunction SP - 551441 EP - 551441 JF - Frontiers in immunology JO - Front Immunol VL - 11 N2 - 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. SN - 1664-3224 UR - https://www.unboundmedicine.com/medline/citation/33250889/Association_Between_Nitric_Oxide_Oxidative_Stress_Eryptosis_Red_Blood_Cell_Microparticles_and_Vascular_Function_in_Sickle_Cell_Anemia_ DB - PRIME DP - Unbound Medicine ER -