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首页> 外文期刊>Redox Biology >Simvastatin reduces circulating oxysterol levels in men with hypercholesterolaemia
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Simvastatin reduces circulating oxysterol levels in men with hypercholesterolaemia

机译：辛伐他汀可降低高胆固醇血症男性的循环氧固醇水平

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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 (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.
机译：氧固醇（OHC）是在血浆中循环的具有生物活性的胆固醇代谢产物，可以通过酶促作用（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。氧固醇比胆固醇更易溶，据报道，其浓度和种类会产生炎症，细胞保护和凋亡作用。尽管氧固醇酯与疾病之间没有一致的关系，但已对痴呆和心血管疾病患者的酯化氧固醇进行了分析。但是，氧固醇酯保留在脂蛋白核心中，可能与无血浆氧固醇的浓度和活性无关。迄今为止，方法学的局限性一直挑战着对游离氧固醇的分析。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，以人血浆中的五种氧固醇为目标，分析物回收率在72％至82 ％和敏感性在5和135？pg / ml之间。一种新方法用于研究辛伐他汀可能降低高胆固醇血症中特定血浆游离氧固醇浓度的假说。招募了20名健康男性志愿者（41-63岁）。 10例无症状且血浆胆固醇> 6.5？mM，而10例健康且血浆胆固醇正常（在高胆固醇血症的中年男性中，通过自氧化产生的氧固醇（但不是酶法）升高了45倍），血浆氧固醇恢复为健康对照者的水平在辛伐他汀干预后，提示辛伐他汀可以直接预防自氧化，或者在血浆胆固醇浓度在正常范围内时自氧化的发生率较低。

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