PMID- 33250889 OWN - NLM STAT- MEDLINE DCOM- 20210430 LR - 20210430 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 11 DP - 2020 TI - Association Between Nitric Oxide, Oxidative Stress, Eryptosis, Red Blood Cell Microparticles, and Vascular Function in Sickle Cell Anemia. PG - 551441 LID - 10.3389/fimmu.2020.551441 [doi] LID - 551441 AB - 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. CI - Copyright (c) 2020 Nader, Romana, Guillot, Fort, Stauffer, Lemonne, Garnier, Skinner, Etienne-Julan, Robert, Gauthier, Cannas, Antoine-Jonville, Tressieres, Hardy-Dessources, Bertrand, Martin, Renoux, Joly, Grau and Connes. FAU - Nader, Elie AU - Nader E AD - Laboratoire Interuniversitaire de Biologie de la Motricite (LIBM) EA7424, Team << Vascular Biology and Red Blood Cell >>, Universite Claude Bernard Lyon 1, Universite de Lyon, Lyon, France. AD - Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France. FAU - Romana, Marc AU - Romana M AD - Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France. AD - Universite des Antilles, Pointe-a-Pitre, France. AD - Universite de Paris, Paris, France. FAU - Guillot, Nicolas AU - Guillot N AD - Laboratoire Carmen Inserm, Universite Claude Bernard Lyon 1, Universite de Lyon, Villeurbanne, France. FAU - Fort, Romain AU - Fort R AD - Laboratoire Interuniversitaire de Biologie de la Motricite (LIBM) EA7424, Team << Vascular Biology and Red Blood Cell >>, Universite Claude Bernard Lyon 1, Universite de Lyon, Lyon, France. AD - Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France. AD - Departement de Medecine Interne, Hopital Edouard Herriot, Hospices Civils de Lyon, Lyon, France. FAU - Stauffer, Emeric AU - Stauffer E AD - Laboratoire Interuniversitaire de Biologie de la Motricite (LIBM) EA7424, Team << Vascular Biology and Red Blood Cell >>, Universite Claude Bernard Lyon 1, Universite de Lyon, Lyon, France. AD - Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France. AD - Centre de Medecine du Sommeil et des Maladies Respiratoires, Hospices Civils de Lyon, Hopital de la Croix Rousse, Lyon, France. FAU - Lemonne, Nathalie AU - Lemonne N AD - Unite Transversale de la Drepanocytose, Hopital de Pointe-a-Pitre, Hopital Ricou, Guadeloupe, France. FAU - Garnier, Yohann AU - Garnier Y AD - Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France. AD - Universite des Antilles, Pointe-a-Pitre, France. AD - Universite de Paris, Paris, France. FAU - Skinner, Sarah Chambers AU - Skinner SC AD - Laboratoire Interuniversitaire de Biologie de la Motricite (LIBM) EA7424, Team << Vascular Biology and Red Blood Cell >>, Universite Claude Bernard Lyon 1, Universite de Lyon, Lyon, France. AD - Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France. FAU - Etienne-Julan, Maryse AU - Etienne-Julan M AD - Unite Transversale de la Drepanocytose, Hopital de Pointe-a-Pitre, Hopital Ricou, Guadeloupe, France. FAU - Robert, Melanie AU - Robert M AD - Erytech Pharma, Lyon, France. FAU - Gauthier, Alexandra AU - Gauthier A AD - Laboratoire Interuniversitaire de Biologie de la Motricite (LIBM) EA7424, Team << Vascular Biology and Red Blood Cell >>, Universite Claude Bernard Lyon 1, Universite de Lyon, Lyon, France. AD - Institut d'Hematologie et d'Oncologie Pediatrique, Hospices Civils de Lyon, Lyon, France. FAU - Cannas, Giovanna AU - Cannas G AD - Laboratoire Interuniversitaire de Biologie de la Motricite (LIBM) EA7424, Team << Vascular Biology and Red Blood Cell >>, Universite Claude Bernard Lyon 1, Universite de Lyon, Lyon, France. AD - Departement de Medecine Interne, Hopital Edouard Herriot, Hospices Civils de Lyon, Lyon, France. FAU - Antoine-Jonville, Sophie AU - Antoine-Jonville S AD - Universite des Antilles, Pointe-a-Pitre, France. FAU - Tressieres, Benoit AU - Tressieres B AD - Centre Investigation Clinique Antilles Guyane, 1424 Inserm, Academic Hospital of Pointe-a-Pitre, Pointe-a-Pitre, Guadeloupe, France. FAU - Hardy-Dessources, Marie-Dominique AU - Hardy-Dessources MD AD - Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France. AD - Universite des Antilles, Pointe-a-Pitre, France. AD - Universite de Paris, Paris, France. FAU - Bertrand, Yves AU - Bertrand Y AD - Institut d'Hematologie et d'Oncologie Pediatrique, Hospices Civils de Lyon, Lyon, France. FAU - Martin, Cyril AU - Martin C AD - Laboratoire Interuniversitaire de Biologie de la Motricite (LIBM) EA7424, Team << Vascular Biology and Red Blood Cell >>, Universite Claude Bernard Lyon 1, Universite de Lyon, Lyon, France. AD - Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France. FAU - Renoux, Celine AU - Renoux C AD - Laboratoire Interuniversitaire de Biologie de la Motricite (LIBM) EA7424, Team << Vascular Biology and Red Blood Cell >>, Universite Claude Bernard Lyon 1, Universite de Lyon, Lyon, France. AD - Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France. AD - Laboratoire de Biochimie et de Biologie Moleculaire, UF de Biochimie des Pathologies erythrocytaires, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, Lyon, France. FAU - Joly, Philippe AU - Joly P AD - Laboratoire Interuniversitaire de Biologie de la Motricite (LIBM) EA7424, Team << Vascular Biology and Red Blood Cell >>, Universite Claude Bernard Lyon 1, Universite de Lyon, Lyon, France. AD - Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France. AD - Laboratoire de Biochimie et de Biologie Moleculaire, UF de Biochimie des Pathologies erythrocytaires, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, Lyon, France. FAU - Grau, Marijke AU - Grau M AD - Molecular and Cellular Sport Medicine, Deutsche Sporthochschule Koln, Koln, Germany. FAU - Connes, Philippe AU - Connes P AD - Laboratoire Interuniversitaire de Biologie de la Motricite (LIBM) EA7424, Team << Vascular Biology and Red Blood Cell >>, Universite Claude Bernard Lyon 1, Universite de Lyon, Lyon, France. AD - Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France. AD - Institut Universitaire de France, Paris, France. LA - eng PT - Clinical Trial PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20201104 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 31C4KY9ESH (Nitric Oxide) SB - IM MH - Adolescent MH - Adult MH - Anemia, Sickle Cell/*blood/pathology MH - Cell-Derived Microparticles/*metabolism/pathology MH - Child MH - Child, Preschool MH - *Eryptosis MH - Erythrocytes, Abnormal/*metabolism/pathology MH - Female MH - Humans MH - Male MH - Nitric Oxide/*blood MH - *Oxidative Stress MH - *Vascular Stiffness PMC - PMC7672038 OTO - NOTNLM OT - TLR4 OT - endothelial cells OT - eryptosis OT - red blood cell microparticles OT - sickle cell anemia OT - vascular dysfunction EDAT- 2020/12/01 06:00 MHDA- 2021/05/01 06:00 PMCR- 2020/01/01 CRDT- 2020/11/30 05:53 PHST- 2020/04/13 00:00 [received] PHST- 2020/10/14 00:00 [accepted] PHST- 2020/11/30 05:53 [entrez] PHST- 2020/12/01 06:00 [pubmed] PHST- 2021/05/01 06:00 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2020.551441 [doi] PST - epublish SO - Front Immunol. 2020 Nov 4;11:551441. doi: 10.3389/fimmu.2020.551441. eCollection 2020.