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High red blood cell nitric oxide synthase activation is not associated with improved vascular function and red blood cell deformability in sickle cell anaemia.
Br J Haematol. 2015 Mar; 168(5):728-36.BJ

Abstract

Human red blood cells (RBC) express an active and functional endothelial-like nitric oxide (NO) synthase (RBC-NOS). We report studies on RBC-NOS activity in sickle cell anaemia (SCA), a genetic disease characterized by decreased RBC deformability and vascular dysfunction. Total RBC-NOS content was not significantly different in SCA patients compared to healthy controls; however, using phosphorylated RBC-NOS-Ser(1177) as a marker, RBC-NOS activation was higher in SCA patients as a consequence of the greater activation of Akt (phosphorylated Akt-Ser(473)). The higher RBC-NOS activation in SCA led to higher levels of S-nitrosylated α- and β-spectrins, and greater RBC nitrite and nitrotyrosine levels compared to healthy controls. Plasma nitrite content was not different between the two groups. Laser Doppler flowmetric experiments demonstrated blunted microcirculatory NO-dependent response under hyperthermia in SCA patients. RBC deformability, measured by ektacytometry, was reduced in SCA in contrast to healthy individuals, and pre-shearing RBC in vitro did not improve deformability despite an increase of RBC-NOS activation. RBC-NOS activation is high in freshly drawn blood from SCA patients, resulting in high amounts of NO produced by RBC. However, this does not result in improved RBC deformability and vascular function: higher RBC-NO is not sufficient to counterbalance the enhanced oxidative stress in SCA.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Grau M
Institute of Cardiovascular Research and Sport Medicine, Department of Molecular and Cellular Sport Medicine, German Sport University Cologne, Cologne, Germany; The German Research Centre of Elite Sport, German Sport University Cologne, Cologne, Germany.
Mozar A
No affiliation info available
Charlot K
No affiliation info available
Lamarre Y
No affiliation info available
Weyel L
No affiliation info available
Suhr F
No affiliation info available
Collins B
No affiliation info available
Jumet S
No affiliation info available
Hardy-Dessources MD
No affiliation info available
Romana M
No affiliation info available
Lemonne N
No affiliation info available
Etienne-Julan M
No affiliation info available
Antoine-Jonville S
No affiliation info available
Bloch W
No affiliation info available
Connes P
No affiliation info available

MeSH

Anemia, Sickle CellEnzyme ActivationErythrocyte DeformabilityErythrocytesFemaleHumansMaleNitric Oxide SynthaseOxidative StressPhosphorylationProto-Oncogene Proteins c-aktSpectrinTyrosine

Pub Type(s)

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

Language

eng

PubMed ID

25316332

Citation

Grau, Marijke, et al. "High Red Blood Cell Nitric Oxide Synthase Activation Is Not Associated With Improved Vascular Function and Red Blood Cell Deformability in Sickle Cell Anaemia." British Journal of Haematology, vol. 168, no. 5, 2015, pp. 728-36.
Grau M, Mozar A, Charlot K, et al. High red blood cell nitric oxide synthase activation is not associated with improved vascular function and red blood cell deformability in sickle cell anaemia. Br J Haematol. 2015;168(5):728-36.
Grau, M., Mozar, A., Charlot, K., Lamarre, Y., Weyel, L., Suhr, F., Collins, B., Jumet, S., Hardy-Dessources, M. D., Romana, M., Lemonne, N., Etienne-Julan, M., Antoine-Jonville, S., Bloch, W., & Connes, P. (2015). High red blood cell nitric oxide synthase activation is not associated with improved vascular function and red blood cell deformability in sickle cell anaemia. British Journal of Haematology, 168(5), 728-36. https://doi.org/10.1111/bjh.13185
Grau M, et al. High Red Blood Cell Nitric Oxide Synthase Activation Is Not Associated With Improved Vascular Function and Red Blood Cell Deformability in Sickle Cell Anaemia. Br J Haematol. 2015;168(5):728-36. PubMed PMID: 25316332.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - High red blood cell nitric oxide synthase activation is not associated with improved vascular function and red blood cell deformability in sickle cell anaemia. AU - Grau,Marijke, AU - Mozar,Anaïs, AU - Charlot,Keyne, AU - Lamarre,Yann, AU - Weyel,Linda, AU - Suhr,Frank, AU - Collins,Bianca, AU - Jumet,Stéphane, AU - Hardy-Dessources,Marie-Dominique, AU - Romana,Marc, AU - Lemonne,Nathalie, AU - Etienne-Julan,Maryse, AU - Antoine-Jonville,Sophie, AU - Bloch,Wilhelm, AU - Connes,Philippe, Y1 - 2014/10/15/ PY - 2014/07/04/received PY - 2014/09/10/accepted PY - 2014/10/16/entrez PY - 2014/10/16/pubmed PY - 2015/4/11/medline KW - blood rheology KW - microcirculation KW - nitric oxide synthase KW - sickle cell anaemia SP - 728 EP - 36 JF - British journal of haematology JO - Br J Haematol VL - 168 IS - 5 N2 - Human red blood cells (RBC) express an active and functional endothelial-like nitric oxide (NO) synthase (RBC-NOS). We report studies on RBC-NOS activity in sickle cell anaemia (SCA), a genetic disease characterized by decreased RBC deformability and vascular dysfunction. Total RBC-NOS content was not significantly different in SCA patients compared to healthy controls; however, using phosphorylated RBC-NOS-Ser(1177) as a marker, RBC-NOS activation was higher in SCA patients as a consequence of the greater activation of Akt (phosphorylated Akt-Ser(473)). The higher RBC-NOS activation in SCA led to higher levels of S-nitrosylated α- and β-spectrins, and greater RBC nitrite and nitrotyrosine levels compared to healthy controls. Plasma nitrite content was not different between the two groups. Laser Doppler flowmetric experiments demonstrated blunted microcirculatory NO-dependent response under hyperthermia in SCA patients. RBC deformability, measured by ektacytometry, was reduced in SCA in contrast to healthy individuals, and pre-shearing RBC in vitro did not improve deformability despite an increase of RBC-NOS activation. RBC-NOS activation is high in freshly drawn blood from SCA patients, resulting in high amounts of NO produced by RBC. However, this does not result in improved RBC deformability and vascular function: higher RBC-NO is not sufficient to counterbalance the enhanced oxidative stress in SCA. SN - 1365-2141 UR - https://www.unboundmedicine.com/medline/citation/25316332/High_red_blood_cell_nitric_oxide_synthase_activation_is_not_associated_with_improved_vascular_function_and_red_blood_cell_deformability_in_sickle_cell_anaemia_ DB - PRIME DP - Unbound Medicine ER -