Hematology and Hemotherapy Center, University of Campinas-UNICAMP, Campinas, Brazil.
Hematology and Hemotherapy Center, University of Campinas-UNICAMP, Campinas, Brazil; Division of Hematology, University of Washington, Seattle, WA, USA.
J Clin Lipidol. 2018 Nov-Dec;12(6):1532-1538. doi: 10.1016/j.jacl.2018.08.002. Epub 2018 Aug 14.
High blood cholesterol is associated with atherogenesis and endothelial dysfunction. The latter is present in hemolytic diseases, such as sickle cell anemia, whose carriers have hypocholesterolemia and low incidence of coronary artery disease.
We aimed to characterize cholesterol fractions in patients with sickle cell disease and explore the relationship among lipoproteins, varying degrees of hemolysis, and its biomarkers.
We recruited 37 healthy individuals, 39 with hemoglobin SC disease, and 40 with sickle cell anemia and quantified cholesterol fractions, heme resulting from hemoglobin breakdown, and its main scavenger protein hemopexin.
Hypocholesterolemia was most significant in patients with sickle cell anemia, and cholesterol levels correlated positively with hemopexin. Nevertheless, patients still had higher relative low-density lipoprotein (LDL) oxidation than healthy subjects. Analysis of lipoproteins isolated by density ultracentrifugation showed that the LDL fraction contained higher concentrations of heme than the high-density lipoprotein (HDL) fraction, whereas HDL contained more hemopexin than LDL, albeit greatly reduced in patients.
Our findings show that the abnormally low lipoprotein levels in sickle cell anemia correlate with hemolysis markers, particularly with hemopexin concentrations, along with significant reduction of this heme scavenger in HDL fractions. This may suggest an important role for HDL in the defense against heme-induced endothelial dysfunction in hemolytic diseases.
高血胆固醇与动脉粥样硬化和内皮功能障碍有关。后者存在于溶血性疾病中,如镰状细胞贫血,其携带者胆固醇水平低,冠心病发病率低。
我们旨在描述镰状细胞病患者的胆固醇分数,并探讨脂蛋白、不同程度的溶血及其生物标志物之间的关系。
我们招募了 37 名健康个体、39 名血红蛋白 SC 疾病患者和 40 名镰状细胞贫血患者,并定量了胆固醇分数、血红蛋白分解产生的血红素及其主要清除蛋白血卟啉。
镰状细胞贫血患者的胆固醇水平最低,胆固醇水平与血卟啉呈正相关。然而,患者的相对低密度脂蛋白(LDL)氧化仍然高于健康受试者。通过密度超速离心分离的脂蛋白分析表明,LDL 部分比高密度脂蛋白(HDL)部分含有更高浓度的血红素,而 HDL 部分比 LDL 部分含有更多的血卟啉,尽管在患者中大大减少。
我们的发现表明,镰状细胞贫血中异常低的脂蛋白水平与溶血标志物相关,特别是与血卟啉浓度相关,同时 HDL 部分中这种血红素清除剂的浓度显著降低。这可能表明 HDL 在溶血性疾病中对血红素诱导的内皮功能障碍具有重要作用。