Hydrogen Activates ATP-Binding Cassette Transporter A1-Dependent Efflux Ex Vivo and Improves High-Density Lipoprotein Function in Patients With Hypercholesterolemia: A Double-Blinded, Randomized, and Placebo-Controlled Trial

Hydrogen Activates ATP-Binding Cassette Transporter A1-Dependent Efflux Ex Vivo and Improves High-Density Lipoprotein Function in Patients With Hypercholesterolemia: A Double-Blinded, Randomized, and Placebo-Controlled Trial
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氢气在体外激活 ATP 结合盒转运蛋白 A1 依赖性流出并改善高胆固醇血症患者的高密度脂蛋白功能:一项双盲、随机和安慰剂对照试验。

DOI:
10.1210/jc.2015-1321
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发表时间:
2015-07-01
影响因子:
5.8
通讯作者:
Qin, Shucun
Qin, Shucun
中科院分区:
医学2区
文献类型:
--
作者:
Song, Guohua;Lin, Quanqiang;Qin, Shucun

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上下文 我们在一项前后对照研究中发现,氢(二氢[H2])可降低潜在代谢综合征患者的血浆低密度脂蛋白(LDL)胆固醇水平,改善高密度脂蛋白(HDL)功能。 目的 本研究的目的是在一项双盲、随机和安慰剂对照试验中进一步表征富氢水(0.9 L/天)对高胆固醇血症患者血浆脂蛋白含量、组成和生物活性的影响及其潜在机制。 设计 这是一项病例对照研究。 设置 背景是中国泰安的周店社区。 患者 共有68例未经治疗的孤立性高胆固醇血症患者被随机分配到饮用富氢水(n = 34)或安慰剂水(n = 34)10周。 结果 从H2组中分离的HDL显示出增强的促进ATP结合盒转运蛋白A1介导的胆固醇体外流出的能力。血浆前-β-HDL水平上调,但血浆HDL-胆固醇水平无变化。此外,其他高密度脂蛋白的功能,在保护LDL氧化,抑制氧化LDL诱导的炎症,并保护内皮细胞氧化LDL诱导的凋亡,都显着改善H2治疗。此外,H2治疗降低血浆总胆固醇(47.06% vs 17.65%)和LDL胆固醇(47.06% vs 23.53%)水平的有效率增加。Western blot分析显示H2组血浆载脂蛋白B100显著降低,载脂蛋白M显著升高。最后,H2处理导致全血浆和HDL颗粒中几种炎症和氧化应激指标的水平显著降低。 结论 H2激活ATP结合盒转运体A1依赖性外排,增强HDL抗动脉粥样硬化功能,并具有有益的降脂作用。目前的研究结果突出了H2在高胆固醇血症和动脉粥样硬化消退中的潜在作用。
CONTEXT We have found that hydrogen (dihydrogen [H2]) decreases plasma low-density lipoprotein (LDL) cholesterol levels and improves high-density lipoprotein (HDL) function in patients with potential metabolic syndrome in a before-after self-controlled study. OBJECTIVE The purpose of this study was to further characterize the effects of H2-rich water (0.9 L/day) on the content, composition, and biological activities of plasma lipoproteins on patients with hypercholesterolemia and their underlying mechanisms in a double-blinded, randomized, and placebo-controlled trial. DESIGN This was a case-control study. SETTING The setting was the Zhoudian community, Tai'an, China. PATIENTS A total of 68 patients with untreated isolated hypercholesterolemia were randomly allocated to either drinking H2-rich water (n = 34) or placebo water (n = 34) for 10 weeks. RESULTS HDL isolated from the H2 group showed an increased ability to promote the ATP-binding cassette transporter A1-mediated cholesterol efflux ex vivo. Plasma pre-β-HDL levels were up-regulated although there were no changes in plasma HDL-cholesterol levels. Moreover, other HDL functions, assessed in protection against LDL oxidation, inhibition of oxidized-LDL-induced inflammation, and protection of endothelial cells from oxidized-LDL-induced apoptosis, were all significantly improved by H2 treatment. In addition, H2 treatment increased the effective rate in down-regulating plasma levels of total cholesterol (47.06% vs 17.65%) and LDL cholesterol (47.06% vs 23.53%). Western blot analysis revealed a marked decrease in apolipoprotein B100 and an increase in apolipoprotein M in plasma of the H2 group. Finally H2 treatment resulted in a significant reduction in the levels of several inflammatory and oxidative stress indicators in whole plasma and HDL particles. CONCLUSIONS H2 activates ATP-binding cassette transporter A1-dependent efflux, enhances HDL antiatherosclerotic functions, and has beneficial lipid-lowering effects. The present findings highlight the potential role of H2 in the regression of hypercholesterolemia and atherosclerosis.