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SICKLE CELL DISEASE: ROLE OF REACTIVE OXYGEN AND NITROGEN METABOLITES
Author(s) -
Wood Katherine C,
Granger D Neil
Publication year - 2007
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2007.04639.x
Subject(s) - xanthine oxidase , endothelial dysfunction , oxidative stress , reactive oxygen species , reactive nitrogen species , nitric oxide , endothelial activation , nadph oxidase , pathogenesis , endothelial stem cell , sickle cell anemia , cell , endothelium , medicine , chemistry , immunology , biology , enzyme , biochemistry , in vitro
SUMMARY1 Sickle cell disease (SCD) is an inherited disorder of haemoglobin synthesis that is associated with significant morbidity and mortality due to sequelae of episodic vaso‐occlusive events: pain crises and multiorgan damage. The microvascular responses to the initiation, progression and resolution of vaso‐occlusive events are consistent with an inflammatory phenotype as suggested by activation of multiple cell types, an oxidatively stressed environment and endothelial cell dysfunction. 2 Decreased anti‐oxidant defences in SCD patients and mice are accompanied by activation of enzymatic (NADPH oxidase, xanthine oxidase) and non‐enzymatic (sickle haemoglobin auto‐oxidation) sources of reactive oxygen species. The resultant oxidative stress leads to dysfunction/activation of arteriolar and venular endothelial cells, resulting in impaired vasomotor function and blood cell–endothelial cell adhesion. 3 Changes in substrate and cofactor availability for endothelial cell nitric oxide synthase may underlie reactive oxygen‐ and nitrogen‐induced events that contribute to SCD‐induced vasculopathy. 4 The emerging role of reactive oxygen and nitrogen species in the pathogenesis of SCD provides a platform for the development of novel agents to treat this painful and lethal disease.