Impact of elevated red blood cell membrane cholesterol in sickle cell anemia patients: Effects of BRN-002, a 2-hydroxypropyl-β-cyclodextrin derivate, on red blood cell lipids, deformability, sickling and hemolysis

IF 2.1 4区医学 Q3 HEMATOLOGY

Blood Cells Molecules and Diseases Pub Date : 2025-06-09 DOI:10.1016/j.bcmd.2025.102939

Claire Bordat , Philippe Connes , Philippe Joly , Solene Poutrel , Carine Halfon-Domenech , Anne Perez , Eric Niesor , Elie Nader

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Abstract

Sickle cell anemia (SCA) patients are characterized by poorly deformable and fragile red blood cells (RBCs). Few studies reported an increased cholesterol content in SCA RBC membrane. However, the consequences of this elevated cholesterol level in the above-mentioned RBC alterations are currently unknown. The aim of this study was to assess, in vitro, the effects of BRN-002 (2-Hydroxypropyl-β-cyclodextrin derivate (HPBCD)), a cholesterol-depleting molecule, on RBC membrane cholesterol, hemolysis and RBC sickling and deformability in SCA patients.

Forty patients with SCA and 10 healthy individuals (AA) were included in the different experiments of the study. SCA RBCs were incubated with BRN-002 and the following parameters were assessed: i) RBC and supernatant cholesterol content; ii) RBC deformability by oxygen-gradient ektacytometry; iii) hemolysis by measuring free hemoglobin concentration.

Results confirmed that SCA patients have increased RBC membrane cholesterol compared to AA. BRN-002 effectively removed cholesterol in SCA RBC membrane and reduced free hemoglobin release during incubation. BRN-002 also increased RBC deformability in hypoxia and decreased the pO₂ at which sickling occurs.

These findings suggest that excess of RBC membrane cholesterol may participate in the typical RBC alterations found in SCA patients. Therefore, interventions focusing on RBC-cholesterol removal may be beneficial for SCA patients.

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镰状细胞性贫血患者红细胞膜胆固醇升高的影响：BRN-002（一种2-羟丙基-β-环糊精衍生物）对红细胞脂质、可变形性、镰状细胞和溶血的影响

镰状细胞性贫血（SCA）患者的特点是红细胞变形不良和脆弱。很少有研究报道SCA红细胞膜中胆固醇含量升高。然而，胆固醇水平升高对上述红细胞改变的影响目前尚不清楚。本研究的目的是在体外评估BRN-002（2-羟丙基-β-环糊精衍生物（HPBCD）），一种胆固醇消耗分子，对SCA患者红细胞膜胆固醇、溶血、红细胞镰状细胞和变形能力的影响。40例SCA患者和10例健康人（AA）被纳入不同的实验。SCA红细胞与BRN-002孵育，并评估以下参数：i)红细胞和上清胆固醇含量；ii)氧梯度分光光度法测定红细胞变形能力；Iii)通过测定游离血红蛋白浓度来溶血。结果证实SCA患者与AA患者相比红细胞膜胆固醇升高。BRN-002有效去除SCA红细胞膜中的胆固醇，并减少培养期间游离血红蛋白的释放。BRN-002还增加了缺氧时红细胞的变形能力，降低了镰状红细胞发生时的pO2。这些发现提示过量的红细胞膜胆固醇可能参与SCA患者中发现的典型红细胞改变。因此，专注于去除红细胞胆固醇的干预措施可能对SCA患者有益。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Blood Cells Molecules and Diseases 医学-血液学

CiteScore

4.90

自引率

0.00%

发文量

审稿时长

14 days

期刊介绍： Blood Cells, Molecules & Diseases emphasizes not only blood cells, but also covers the molecular basis of hematologic disease and studies of the diseases themselves. This is an invaluable resource to all those interested in the study of hematology, cell biology, immunology, and human genetics.