Plasma monomeric ApoA1 and high-density lipoprotein bound ApoA1 are markedly decreased and associated with low levels of lipophilic antioxidants in sickle cell disease: A potential new pathway for therapy

IF 2.3 3区 医学 Q2 HEMATOLOGY
Eric J. Niesor, Anne Perez, Serge Rezzi, Andrew Hodgson, Stephane Canarelli, Gregoire Millet, Tadej Debevec, Claire Bordat, Elie Nader, Philippe Connes
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引用次数: 0

Abstract

Patients with sickle cell disease (SCD) exhibit high levels of reactive oxygen species and low plasma levels of lipophilic antioxidants, which may contribute to end-organ damage and disease sequelae. Apolipoprotein A1, the major apolipoprotein of high-density lipoprotein (HDL), is mainly secreted by the intestine and liver in the form of monomeric ApoA1 (mApoA1) present in plasma. Cholesterol and α-tocopherol are delivered to ApoA1 via the ATP-binding cassette transporter, subfamily A, member 1 (ABCA1). We measured cholesterol, mApoA1, ApoA1, and lipophilic antioxidants in the plasma of 17 patients with SCD and 40 healthy volunteers. Mean HDL cholesterol (-C) levels in SCD patients and healthy subjects were 59.3 and 48.1 mg/dL, respectively, and plasma lutein, zeaxanthin, and α-tocopherol were 64.0%, 68.7%, and 9.1% lower, respectively. To compare SCD to healthy subjects with similar HDL-C, we also performed subgroup analyses of healthy subjects with HDL-C above or below the mean. In SCD, the mApoA1 level was 30.4 μg/mL; 80% lower than 141 μg/mL measured in healthy volunteers with similar HDL-C (56.7 mg/dL). The mApoA1 level was also 38.4% greater in the higher versus lower HDL-C subgroups (p = .002). In the higher HDL-C subgroup, lutein and zeaxanthin transported by HDL were 48.9% (p = .01) and 41.9% (p = .02) higher, respectively, whereas α-tocopherol was 31.7% higher (p = .003), compared to the lower HDL-C subgroup. Plasma mApoA1 may be a marker of the capacity of HDL to capture and deliver liposoluble antioxidants, and treatments which raise HDL may benefit patients with high oxidative stress as exemplified by SCD.

Abstract Image

镰状细胞病患者血浆单体载脂蛋白A1和与高密度脂蛋白结合的载脂蛋白A1明显减少,并与亲脂性抗氧化剂水平低有关:潜在的治疗新途径。
镰状细胞病(SCD)患者表现出高水平的活性氧和低水平的血浆亲脂性抗氧化剂,这可能会导致终末器官损伤和疾病后遗症。载脂蛋白 A1 是高密度脂蛋白(HDL)的主要载脂蛋白,主要由肠道和肝脏分泌,以单体载脂蛋白 A1(mApoA1)的形式存在于血浆中。胆固醇和α-生育酚通过 ATP 结合盒转运体 A 亚家族成员 1(ABCA1)输送到载脂蛋白 A1。我们测量了 17 名 SCD 患者和 40 名健康志愿者血浆中的胆固醇、mApoA1、载脂蛋白 A1 和亲脂抗氧化剂。SCD患者和健康受试者的平均高密度脂蛋白胆固醇(-C)水平分别为59.3和48.1毫克/分升,血浆中的叶黄素、玉米黄质和α-生育酚分别降低了64.0%、68.7%和9.1%。为了将 SCD 与具有相似 HDL-C 的健康受试者进行比较,我们还对 HDL-C 高于或低于平均值的健康受试者进行了亚组分析。在 SCD 患者中,mApoA1 水平为 30.4 μg/mL;比具有相似 HDL-C 的健康志愿者(56.7 mg/dL)所测得的 141 μg/mL 低 80%。高 HDL-C 亚组的 mApoA1 水平比低 HDL-C 亚组高 38.4%(p = .002)。在高 HDL-C 亚组中,与低 HDL-C 亚组相比,HDL 转运的叶黄素和玉米黄质分别高出 48.9% (p = .01) 和 41.9% (p = .02),而α-生育酚则高出 31.7% (p = .003)。血浆 mApoA1 可能是高密度脂蛋白捕获和输送脂溶性抗氧化剂能力的标志,提高高密度脂蛋白的治疗方法可能对 SCD 等高氧化应激患者有益。
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来源期刊
CiteScore
5.50
自引率
0.00%
发文量
168
审稿时长
4-8 weeks
期刊介绍: European Journal of Haematology is an international journal for communication of basic and clinical research in haematology. The journal welcomes manuscripts on molecular, cellular and clinical research on diseases of the blood, vascular and lymphatic tissue, and on basic molecular and cellular research related to normal development and function of the blood, vascular and lymphatic tissue. The journal also welcomes reviews on clinical haematology and basic research, case reports, and clinical pictures.
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