Development and Clinical Application of an Enzyme-Linked Immunosorbent Assay for Oxidized High-Density Lipoprotein.
Development and Clinical Application of an Enzyme-Linked Immunosorbent Assay for Oxidized High-Density Lipoprotein.
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DOI：
10.5551/jat.56887
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发表时间：
2021-07-01
影响因子：
4.4
通讯作者：
Yamashita S
中科院分区：
文献类型：
--
作者：
Okada T;Sumida M;Ohama T;Katayama Y;Saga A;Inui H;Kanno K;Masuda D;Koseki M;Nishida M;Sakata Y;Yamashita S
目的：HDL颗粒具有多种抗动脉粥样硬化的功能，而动脉粥样硬化患者的HDL被证明是功能障碍的。HDL功能失调的一种可能机制是其组分的氧化。然而，由于缺乏可靠的检测系统，氧化HDL（Ox-HDL）仍有待深入研究。 研究方法：我们已经开发了一种新的夹心酶联免疫吸附试验（ELISA）的Ox-HDL通过使用FOH 1a/DLH 3抗体，它可以特异性地识别氧化磷脂酰胆碱，HDL磷脂（HDL-PL）的主要成分。我们将1 mg/L HDL-PL的强制氧化定义为1 U/L Ox-HDL。我们评估了血脂正常的健康受试者（n =94）和血脂异常患者（n =177）的血清Ox-HDL水平。 结果：批内和批间变异系数分别为12.5%和13.5%。在健康受试者中，血清Ox-HDL水平为28.5±5.0（平均值±SD）U/L。由于Ox-HDL水平与HDL-PL中度相关（r=0.59），我们还评估了Ox-HDL/HDL-PL比率，其代表HDL颗粒中氧化磷脂的比例。在血脂异常患者中，Ox-HDL水平变化很大，范围为7.2 ~ 62.1U/L，特别是胆固醇酯转移蛋白缺乏引起的高脂蛋白血症患者，Ox-HDL水平极高（50.4±13.3U/L）。对于家族性高胆固醇血症患者，与未使用普罗布考的患者相比，使用普罗布考（一种有效的抗氧化和抗高血脂药物）治疗的患者显示出明显较低的Ox-HDL（16.2±5.8 vs. 30.2±5.4，p <0.001）和Ox-HDL/HDL-PL比值（0.200±0.035 vs. 0.229±0.031，p =0.015）。 结论：我们建立了一种新的Ox-HDL的夹心ELISA，这可能是一个有用的和简单的策略来评估HDL的功能，虽然这种Ox-HDL ELISA和HDL胆固醇流出能力的测定之间的比较研究仍有待完成。我们的研究结果表明，普罗布考治疗可能与较低的Ox-HDL水平。
Aims: HDL particles have various anti-atherogenic functions, whereas HDL from atherosclerotic patients was demonstrated to be dysfunctional. One possible mechanism for the formation of dysfunctional HDL is the oxidation of its components. However, oxidized HDLs (Ox-HDLs) remain to be well investigated due to lack of reliable assay systems. Methods: We have developed a novel sandwich enzyme-linked immunosorbent assay (ELISA) for Ox-HDL by using the FOH1a/DLH3 antibody, which can specifically recognize oxidized phosphatidylcholine, a major component of HDL phospholipid (HDL-PL). We defined forced oxidation of 1 mg/L HDL-PL as 1 U/L Ox-HDL. We assessed serum Ox-HDL levels of normolipidemic healthy subjects ( n =94) and dyslipidemic patients ( n =177). Results: The coefficients of variation of within-run and between-run assays were 12.5% and 13.5%. In healthy subjects, serum Ox-HDL levels were 28.5±5.0 (mean±SD) U/L. As Ox-HDL levels were moderately correlated with HDL-PL (r=0.59), we also evaluated the Ox-HDL/HDL-PL ratio, which represents the proportion of oxidized phospholipids in HDL particles. In dyslipidemic patients, Ox-HDL levels were highly variable and ranged from 7.2 to 62.1U/L, and were extremely high (50.4±13.3U/L) especially in patients with hyperalphalipoproteinemia due to cholesteryl ester transfer protein deficiency. Regarding patients with familial hypercholesterolemia, those treated with probucol, which is a potent anti-oxidative and anti-hyperlipidemic drug, showed significantly lower Ox-HDL (16.2±5.8 vs. 30.2±5.4, p ＜0.001) and Ox-HDL/HDL-PL ratios (0.200±0.035 vs. 0.229±0.031, p =0.015) than those without probucol. Conclusion: We have established a novel sandwich ELISA for Ox-HDL, which might be a useful and easy strategy to evaluate HDL functionality, although the comparison study between this Ox-HDL ELISA and the assay of HDL cholesterol efflux capacity remains to be done. Our results indicated that probucol treatment may be associated with lower Ox-HDL levels.
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影响因子：
8.7
作者：
Hirano, K;Yamashita, S;Matsuzawa, Y
通讯作者：
Matsuzawa, Y
影响因子：
158.5
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
Patsch, W
影响因子：
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作者：
Gomaraschi, Monica;Ossoli, Alice;Calabresi, Laura
通讯作者：
Calabresi, Laura