OBJECTIVE: Sickle cell disease (SCD) is characterized by extensive hemolysis, increased cellular adhesion, and vaso-occlusion. Tissues from sickle patients express heme oxygenase-1 (HO-1), the enzyme that degrades free heme/hemoglobin to the signaling molecule carbon monoxide, and the antioxidants biliverdin/bilirubin. Here, we examined the HO response in endothelial cells exposed to human sickle blood and determined whether this response is beneficial for SCD. METHODS AND RESULTS: We measured HO activity in human and bovine aortic endothelial cells incubated with human sickle or normal blood. Sickle blood increased HO activity, which was enhanced by hypoxia and was caused mainly by the red cell components of sickle blood. Oxidized hemoglobin was higher in sickle blood and increased markedly over time. Interestingly, HO activity correlated inversely with patients' hemoglobin levels and positively with bilirubin and lactate dehydrogenase. HO-1 induction, exogenous biliverdin, or carbon monoxide markedly decreased adhesion of sickle blood to the endothelium, and sickle red cells partially inhibited relaxation mediated by carbon monoxide in isolated aortas. CONCLUSIONS: Our results highlight important associations between SCD and HO byproducts, which may counteract vascular complications of SCD.
OBJECTIVE: Sickle cell disease (SCD) is characterized by extensive hemolysis, increased cellular adhesion, and vaso-occlusion. Tissues from sickle patients express heme oxygenase-1 (HO-1), the enzyme that degrades free heme/hemoglobin to the signaling molecule carbon monoxide, and the antioxidants biliverdin/bilirubin. Here, we examined the HO response in endothelial cells exposed to human sickle blood and determined whether this response is beneficial for SCD. METHODS AND RESULTS: We measured HO activity in human and bovine aortic endothelial cells incubated with human sickle or normal blood. Sickle blood increased HO activity, which was enhanced by hypoxia and was caused mainly by the red cell components of sickle blood. Oxidized hemoglobin was higher in sickle blood and increased markedly over time. Interestingly, HO activity correlated inversely with patients' hemoglobin levels and positively with bilirubin and lactate dehydrogenase. HO-1 induction, exogenous biliverdin, or carbon monoxide markedly decreased adhesion of sickle blood to the endothelium, and sickle red cells partially inhibited relaxation mediated by carbon monoxide in isolated aortas. CONCLUSIONS: Our results highlight important associations between SCD and HO byproducts, which may counteract vascular complications of SCD.
Authors: Hwa Jin Jang; Young Min Kim; Konstantin Tsoyi; Eun Jung Park; Young Soo Lee; Hye Jung Kim; Jae Heun Lee; Yeonsoo Joe; Hun Taeg Chung; Ki Churl Chang Journal: Antioxid Redox Signal Date: 2012-04-18 Impact factor: 8.401
Authors: Stéphane M Camus; João A De Moraes; Philippe Bonnin; Paul Abbyad; Sylvain Le Jeune; François Lionnet; Laurent Loufrani; Linda Grimaud; Jean-Christophe Lambry; Dominique Charue; Laurent Kiger; Jean-Marie Renard; Claire Larroque; Hervé Le Clésiau; Alain Tedgui; Patrick Bruneval; Christina Barja-Fidalgo; Antigoni Alexandrou; Pierre-Louis Tharaux; Chantal M Boulanger; Olivier P Blanc-Brude Journal: Blood Date: 2015-03-31 Impact factor: 22.113
Authors: Edward Gomperts; John D Belcher; Leo E Otterbein; Thomas D Coates; John Wood; Brett E Skolnick; Howard Levy; Gregory M Vercellotti Journal: Am J Hematol Date: 2017-04-29 Impact factor: 10.047