Department of Surgical Research, Northwick Park Institute for Medical Research, Harrow, Middlesex, United Kingdom.
Arterioscler Thromb Vasc Biol. 2010 Feb;30(2):305-12. doi: 10.1161/ATVBAHA.109.196360. Epub 2009 Dec 3.
Sickle cell disease (SCD) is characterized by extensive hemolysis, increased cellular adhesion, and vaso-occlusion. Tissues from sickle patients express heme oxygenase-1 (HO-1), the enzyme that degrades free heme/hemoglobin to the signaling molecule carbon monoxide, and the antioxidants biliverdin/bilirubin. Here, we examined the HO response in endothelial cells exposed to human sickle blood and determined whether this response is beneficial for SCD.
We measured HO activity in human and bovine aortic endothelial cells incubated with human sickle or normal blood. Sickle blood increased HO activity, which was enhanced by hypoxia and was caused mainly by the red cell components of sickle blood. Oxidized hemoglobin was higher in sickle blood and increased markedly over time. Interestingly, HO activity correlated inversely with patients' hemoglobin levels and positively with bilirubin and lactate dehydrogenase. HO-1 induction, exogenous biliverdin, or carbon monoxide markedly decreased adhesion of sickle blood to the endothelium, and sickle red cells partially inhibited relaxation mediated by carbon monoxide in isolated aortas.
Our results highlight important associations between SCD and HO byproducts, which may counteract vascular complications of SCD.
镰状细胞病（SCD）的特征是广泛溶血、细胞黏附增加和血管阻塞。镰状细胞病患者的组织表达血红素加氧酶-1（HO-1），该酶可将游离血红素/血红蛋白降解为信号分子一氧化碳和抗氧化剂胆绿素/胆红素。在这里，我们研究了暴露于人镰状血的内皮细胞中的 HO 反应，并确定了这种反应是否对 SCD 有益。
我们测量了与人或牛主动脉内皮细胞孵育的人镰状或正常血液中的 HO 活性。镰状血增加了 HO 活性，缺氧会增强这种活性，主要是由镰状血的红细胞成分引起的。氧化血红蛋白在镰状血中含量更高，且随着时间的推移显著增加。有趣的是，HO 活性与患者的血红蛋白水平呈负相关，与胆红素和乳酸脱氢酶呈正相关。HO-1 诱导、外源性胆绿素或一氧化碳显著降低了镰状血在内皮细胞上的黏附，镰状红细胞部分抑制了分离主动脉中一氧化碳介导的舒张。
我们的结果突出了 SCD 和 HO 副产物之间的重要关联，这可能抵消了 SCD 的血管并发症。
