The endothelial biology of sickle cell disease: inflammation and a chronic vasculopathy

Microcirculation. 2004 Mar;11(2):129-51.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Anemia, Sickle Cell / genetics
  • Anemia, Sickle Cell / metabolism
  • Anemia, Sickle Cell / pathology*
  • Anemia, Sickle Cell / physiopathology*
  • Chronic Disease
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiopathology*
  • Erythrocytes, Abnormal / metabolism
  • Genotype
  • Humans
  • Inflammation / genetics
  • Inflammation / metabolism
  • Inflammation / physiopathology
  • Leukocytes / metabolism
  • Reperfusion Injury / genetics
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / physiopathology*
  • Vascular Diseases / genetics
  • Vascular Diseases / metabolism
  • Vascular Diseases / physiopathology