Hebbel Robert P, Osarogiagbon Raymond, Kaul Dhananjay
Vascular Biology Center and Division of Hematology-Oncology-Transplantation, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
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.
血红蛋白中的单个氨基酸替换构成了镰状细胞贫血的分子基础,但相应临床疾病的演变极其复杂,可能涉及多种致病因素。镰状细胞病本质上是一种炎症状态,内皮细胞被激活,这可能是由于再灌注损伤生理学的直接影响以及黏附的红细胞和白细胞的长期骚扰所致。该疾病还涉及血管生成倾向增强、凝血激活、血管调节紊乱以及慢性血管病变的一个组成部分。镰状细胞贫血确实是一种内皮细胞疾病,内皮功能的基因差异很可能有助于控制其惊人的表型多样性。