Association between oxidative stress and vascular reactivity in children with sickle cell anaemia and sickle haemoglobin C disease

Abstract

Oxidative stress and haemolysis-associated nitric oxide (NO) depletion plays a crucial role in the development of vasculopathy in sickle cell anaemia (SS). However it remains unknown whether oxidative stress and haemolysis levels influence vascular function in patients with sickle haemoglobin C disease (SC). Microvascular response to heat (using Laser Doppler flowmetry on finger), oxidative stress biomarkers, NO metabolites, endothelin-1 and haematological parameters were compared between patients with SS and SC. Vascular function, oxidative and nitrosative markers were also measured in healthy (AA) children. SS and SC had increased plasma advanced oxidation protein products (AOPP), malondialdehyde, plasma antioxidant activities and NO end products, compared to AA. SC had lower catalase activity compared to AA and SS. Haemolytic rate, glutathione peroxidase and nitrotyrosine concentrations were significantly increased in children with SS compared to SC and AA. SS and SC had impaired microvascular reactivity compared to AA. In SS, the plateau phase of the response to local thermal heating was negatively associated with nitrotyrosine and AOPP. No association between vascular function parameters and oxidative stress markers was observed in SC. Mild haemolysis in SC, compared to SS, may limit oxidative and nitrosative stress and could explain the better preserved microvascular function in this group.

The Red Blood Cell—Inflammation Vicious Circle in Sickle Cell Disease

“…As previously discussed, oxidative stress is increased in SCD, both in plasma and RBC (15,82,(89)(90)(91)(92), with a further rise during painful vaso-occlusive crises (68). Through its effects on the membrane of RBCs (i.e., lipid peroxidation and protein oxidation) and caspase 3 activation (93, 94), oxidative stress is a key modulator of RBC rheological properties.…”

Association Between Nitric Oxide, Oxidative Stress, Eryptosis, Red Blood Cell Microparticles, and Vascular Function in Sickle Cell Anemia

“…Indeed, patients with SCA suffer from chronic hemolytic anemia and repeated vaso-occlusive crises ( 1 ). Accumulating evidence suggests that chronic hemolysis, enhanced oxidative stress and decreased bioavailability of nitric oxide (NO) are at the origin of the vascular dysfunction observed in patients with SCA ( 2 – 4 ), which could be involved in the pathogenesis of several acute and chronic complications ( 3 ). In addition, heme released by red blood cells into the plasma could play a role in vascular dysfunction by promoting inflammation through the activation of Toll Like Receptor 4 (TLR4) ( 5 ).…”

Influence of Oxidative Stress Biomarkers and Genetic Polymorphisms on the Clinical Severity of Hydroxyurea-Free Senegalese Children with Sickle Cell Anemia

“…For instance, Biswal et al [ 11 ] reported lower superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activities in SCA children compared to controls. Mockesch et al [ 7 ] found higher SOD activity in SCA than in healthy children and similar CAT and GPX activities in the two populations. Renoux et al [ 12 ] described higher SOD and lower GPX activities but similar CAT activity in a group of SCA children compared to a control group.…”

“…Oxidative stress is enhanced in SCA and would also play a major role in the pathophysiology of the disease by promoting red blood cell (RBC) damage, inflammation, and endothelial-vascular dysfunction [ 1 , 2 , 3 , 4 ]. Elevated advanced oxidation protein products (AOPP) and malondialdehyde (MDA) concentrations have been consistently reported in patients with SCA, both at a systemic or RBC level [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. As a consequence, it would be expected that RBC and plasma from patients with SCA exhibit decreased antioxidant capacities.…”