Simvastatin reduces circulating oxysterol levels in men with hypercholesterolaemia.
Simvastatin reduces circulating oxysterol levels in men with hypercholesterolaemia.
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DOI：
10.1016/j.redox.2018.02.014
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发表时间：
2018-06
期刊：
影响因子：
11.4
通讯作者：
Griffiths HR
中科院分区：
文献类型：
--
作者：
Dias IHK;Milic I;Lip GYH;Devitt A;Polidori MC;Griffiths HR
氧甾醇 (OHC) 是在血浆中循环的具有生物活性的胆固醇代谢物，可通过酶促形成（例如 24S-OHC、25-OHC 和 27-OHC）或通过自氧化机制（例如 7-酮胆固醇、7β-OHC 和 25-OHC）形成。氧甾醇比胆固醇更易溶解，据报道根据浓度和种类可发挥炎症、细胞保护和细胞凋亡作用。尽管氧甾醇酯与疾病之间没有一致的关系，但已经对痴呆症和心血管疾病患者的酯化氧甾醇进行了分析。然而，氧甾醇酯保留在脂蛋白核心中，可能与血浆游离氧甾醇的浓度和活性无关。迄今为止，方法学的局限性对游离氧甾醇的分析提出了挑战。我们开发了一种快速、灵敏且特异的定量 LC-MS/MS 多反应监测 (MRM) 方法，可针对人血浆中的五种氧甾醇进行检测，分析物回收率在 72% 至 82% 之间，灵敏度在 5 至 135pg/ml 之间。使用一种新方法来研究辛伐他汀可能降低高胆固醇血症中特定血浆游离氧甾醇浓度的假设。招募20名健康男性志愿者（年龄41-63岁）；其中 10 名无症状，血浆胆固醇高 >6.5mM，10 名健康，血浆胆固醇正常 (<6.5mM)。辛伐他汀（40 毫克/天）用于治疗高胆固醇血症患者。在基线时和三个月后从两组中采集血浆样本。三个月后，辛伐他汀使血浆胆固醇降低约 35% (p<0.05)。在高胆固醇血症的中年男性中，通过自动氧化（但不是酶促氧化）产生的氧甾醇升高高达 45 倍。辛伐他汀干预后，血浆氧甾醇恢复到健康对照的水平，这表明辛伐他汀可以直接预防自动氧化，或者当血浆胆固醇浓度在正常范围内时，自动氧化不太常见。
Oxysterols (OHC) are biologically active cholesterol metabolites circulating in plasma that may be formed enzymatically (e.g. 24S-OHC, 25-OHC and 27-OHC) or by autoxidative mechanisms (e.g. 7-ketocholesterol, 7β-OHC and 25-OHC). Oxysterols are more soluble than cholesterol and are reported to exert inflammatory, cytoprotective and apoptotic effects according to concentration and species. Esterified oxysterols have been analysed in people with dementia and cardiovascular diseases although there is no consistent relationship between oxysterol esters and disease. However, oxysterol esters are held in lipoprotein core and may not relate to the concentration and activity of plasma free oxysterols. Methodological limitations have challenged the analysis of free oxysterols to date. We have developed a fast, sensitive and specific quantitative LC-MS/MS, multiple reaction monitoring (MRM) method to target five oxysterols in human plasma with analyte recoveries between 72% and 82% and sensitivities between 5 and 135 pg/ml. A novel method was used to investigate the hypothesis that simvastatin may reduce the concentrations of specific plasma free oxysterols in hypercholesterolaemia. Twenty healthy male volunteers were recruited (aged 41–63 years); ten were asymptomatic with high plasma cholesterol > 6.5 mM and ten were healthy with normal plasma cholesterol (< 6.5 mM). Simvastatin (40 mg/day) was prescribed to those with hypercholesterolaemia. Plasma samples were taken from both groups at baseline and after three months. Simvastatin reduced plasma cholesterol by ~35% (p < 0.05) at the end of three months. Oxysterols generated by autoxidation (but not enzymatically) were elevated up to 45 fold in hypercholesterolaemic midlife men. Plasma oxysterols were restored to those of healthy controls after simvastatin intervention suggesting that autoxidation is either prevented by simvastatin directly or that autoxidation is less prevalent when plasma cholesterol concentrations are within the normal range.
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影响因子：
5.3
作者：
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通讯作者：
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影响因子：
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