Human Sickle Cell Blood Modulates Endothelial Heme Oxygenase Activity Effects on Vascular Adhesion and Reactivity
Human Sickle Cell Blood Modulates Endothelial Heme Oxygenase Activity Effects on Vascular Adhesion and Reactivity
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DOI：
10.1161/atvbaha.109.196360
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发表时间：
2010-02-01
影响因子：
8.7
通讯作者：
Motterlini, Roberto
中科院分区：
文献类型：
--
作者：
Bains, Sandip K.;Foresti, Roberta;Motterlini, Roberto
镰状细胞病（SCD）的特征是广泛的溶血，细胞粘附增加和血管闭塞。镰状患者的组织表达血红素加氧酶-1（HO-1），该酶将游离血红素/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HO反应在内皮细胞暴露于人镰状血，并确定这种反应是否是有益的SCD。方法和结果，我们测量了HO活性在人类和牛主动脉内皮细胞与人类镰状或正常血液孵育。镰状血增加HO活性，这是由缺氧增强，主要是由镰状血的红细胞成分。氧化血红蛋白在镰状血中较高，并随时间显著增加。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的诱导，外源性胆绿素，或一氧化碳显着降低镰状血内皮细胞的粘附，镰状红细胞部分抑制一氧化碳介导的松弛在孤立的arrhythm.Conclusions，我们的研究结果突出了SCD和HO副产品，这可能会抵消SCD的血管并发症之间的重要关联。（Arterioscler Thromb Vasc Biol.2010; 30：305 - 312.）
Objective-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.Methods and Results-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.Conclusions-Our results highlight important associations between SCD and HO byproducts, which may counteract vascular complications of SCD. (Arterioscler Thromb Vasc Biol. 2010;30:305-312.)