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The Endothelial Biology of Sickle Cell Disease: Inflammation and a Chronic Vasculopathy


  • This work was supported by the National Institutes of Health grants HL30160, HL55552, and HL68970.

Address correspondence to Dr. Robert P. Hebbel, Department of Medicine, University of Minnesota Medical School, MMC 480, 420 Delaware St. SE, Minneapolis, MN 55455, USA. E-mail:


A single amino acid substitution in hemoglobin comprises the molecular basis for sickle cell anemia, but evolution of the corresponding clinical disease is extraordinarily complicated and likely involves multiple pathogenic factors. Sickle disease is fundamentally an inflammatory state, with activation of the endothelium, probably through proximate effects of reperfusion injury physiology and chronic molestation by adherent red cells and white cells. The disease also involves enhanced angiogenic propensity, activation of coagulation, disordered vasoregulation, and a component of chronic vasculopathy. Sickle cell anemia is truly an endothelial disease, and it is likely that genetic differences in endothelial function help govern its astonishing phenotypic diversity.