title: Hypoxia/reoxygenation stress increases markers of vaso-occlusive crisis in sickle SAD mice.
abstract: In sickle cell disease, the factors involved in vasoocclusive crisis (VOC) include the sickling of red blood cells (RBC), abnormal blood rheology, inflammation, vascular adhesion, oxidative stress, coagulation, and vascular tone modulation. The aim of this study was to further characterize the molecular response of some factors involved in VOC by inducing a hypoxia/reoxygenation stress in sickle SAD mice. Results show that a hypoxia/reoxygenation stress in SAD mice can induce: (i) a decrease in reticulocytes count, and mean corpuscular volume along with an increase in lactate dehydrogenase (p = 0.07) and sickled cell proportion; (ii) a significant increase in lung VCAM-1, ICAM-1, IL-1β, ET-1, eNOS, and TF mRNA associated with an increase in VCAM-1 expression on lung endothelium; (iii) a rise in cardiac oxidative stress with increased lipid oxidation and decreased anti-oxidant enzyme activities, and (iv) an increase in plasma TNF-α and IL-6 and a decrease in plasma ET-1. In SAD mice, hypoxia/reoxygenation stress induces hemolysis that, together with oxidative stress, inflammation, vascular adhesion, and coagulation, may induce vascular occlusion and consequently RBC sickling. The present results give the kinetics of VOC molecular markers in SAD mice which may aid in testing the efficiency of new therapeutic processes against VOC.
authors.affiliation: EA Center of Research and Innovation on Sports, University Claude Bernard Lyon 1, University of Lyon, Lyon, France.
authors.forename: Emeline
authors.initials: E
authors.lastname: Aufradet
authors.forename: Geneviève
authors.initials: G
authors.lastname: DeSouza
authors.forename: Vanessa
authors.initials: V
authors.lastname: Bourgeaux
authors.forename: Amine
authors.initials: A
authors.lastname: Bessaad
authors.forename: Yannick
authors.initials: Y
authors.lastname: Campion
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Canet-Soulas
authors.forename: Vincent
authors.initials: V
authors.lastname: Pialoux
authors.forename: Erica N
authors.initials: EN
authors.lastname: Chirico
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Chevrier
authors.forename: Yann
authors.initials: Y
authors.lastname: Godfrin
authors.forename: Cyril
authors.initials: C
authors.lastname: Martin
mesh_terms: D000755:Anemia, Sickle Cell / Q000097:blood* / Q000150:complications* / Q000473:pathology; D000818:Animals; D002452:Cell Count; D006461:Hemolysis; D006801:Humans; D000860:Hypoxia / Q000150:complications*; D007249:Inflammation / Q000097:blood; D008168:Lung / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018384:Oxidative Stress; D012156:Reticulocytes / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis; D014652:Vascular Diseases / Q000209:etiology*
chemical_list: D019010:Vascular Cell Adhesion Molecule-1