High red blood cell nitric oxide synthase activation is not associated with improved vascular function and red blood cell deformability in sickle cell anaemia

Marijke Grau, Anaïs Mozar, Keyne Charlot, Yann Lamarre, Linda Weyel, Frank Suhr, Bianca Collins, Stéphane Jumet, Marie Dominique Hardy-Dessources, Marc Romana, Nathalie Lemonne, Maryse Etienne-Julan, Sophie Antoine-Jonville, Wilhelm Bloch, Philippe Connes

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Summary: 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-Ser1177 as a marker, RBC-NOS activation was higher in SCA patients as a consequence of the greater activation of Akt (phosphorylated Akt-Ser473). 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.

Original languageEnglish (US)
Pages (from-to)728-736
Number of pages9
JournalBritish journal of haematology
Volume168
Issue number5
DOIs
StatePublished - Mar 1 2015

Keywords

  • Blood rheology
  • Microcirculation
  • Nitric oxide synthase
  • Sickle cell anaemia

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