The endothelial biology of sickle cell disease: inflammation and a chronic vasculopathy.
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.
Hebbel
Robert P
RP
Vascular Biology Center and Division of Hematology-Oncology-Transplantation, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA. hebbe001@umn.edu
Osarogiagbon
Raymond
R
Kaul
Dhananjay
D
D000755:Anemia, Sickle Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D002908:Chronic Disease; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D004913:Erythrocytes, Abnormal / Q000378:metabolism; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D007962:Leukocytes / Q000378:metabolism; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D014652:Vascular Diseases / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology