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 Printable version |
Insights into vascular pathobiology of sickle cell disease |
Hématologie. Volume 15, Number 6, 446-57, novembre-décembre 2009, Revue
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 Résumé
Article gratuit
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Author(s) : Dhananjay K Kaul |
Summary : This review focuses on recent insights into vascular pathobiology in sickle cell disease derived from studies in sickle patients and transgenic sickle mouse models. Essentially, the events originating from the primary defect of sickle cell disease (i.e., hemoglobin S polymerization and intravascular sickling) lead to a spectrum of pathologies including red cell abnormalities, reperfusion injury, hemoglobin S autoxidation and hemolysis, which contribute to increased oxidative stress and reduced nitric oxide (NO) bioavailability. The premise of this review is that the interaction between oxidative stress and limited NO bioavailability is a major source of endothelial dysfunction, inflammation, abnormal blood cell-endothelium interaction and vascular pathobiology. Oxidative stress and hemolysis accelerate consumption/inactivation of endothelial-derived NO that leads to vascular resistance to NO-mediated vasoactive stimuli. This review also draws attention to the role of NO-independent factors in vasoregulation, and describes the mechanisms involved in vascular adaptations (e.g., induction of non-NO vasodilators), both in the human sickle cell disease and transgenic sickle mouse models. We also discuss intravital microvascular findings in sickle mouse models that have contributed to the understanding of vascular regulation in this disease. |
Keywords : sickle cell disease, humans, transgenic mice, vascular pathology, endothelium, NO |
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