High plasma thiocyanate levels are associated with enhanced myeloperoxidase-induced thiol oxidation and long-term survival in subjects following a first myocardial infarction
High plasma thiocyanate levels are associated with enhanced myeloperoxidase-induced thiol oxidation and long-term survival in subjects following a first myocardial infarction
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DOI：
10.3109/10715762.2014.947286
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发表时间：
2014-10-01
影响因子：
3.3
通讯作者：
Davies, M. J.
中科院分区：
文献类型：
--
作者：
Nedoboy, P. E.;Morgan, P. E.;Davies, M. J.
髓过氧化物酶（MPO）水平升高与不良心血管预后相关。MPO利用H2O2分别由氯离子和硫氰酸盐（SCN-）离子生成HOCl和HOSCN等氧化剂。SCN-是首选的衬底。这种阴离子的升高减少HOCl的生成，增加HOSCN的形成，HOSCN是一种硫醇特异性氧化剂。这种变化可能与SCN水平升高的人有关，例如吸烟者。在这项回顾性研究中，我们研究了176例首次心肌梗死住院患者（74例不吸烟者，46例吸烟者和56例既往吸烟者）血浆MPO和SCN水平升高是否会因HOSCN形成增加而增加硫醇氧化，并影响长期生存。与非吸烟者或既往吸烟者相比，吸烟者血浆硫醇含量没有明显改变。然而，在总体人群（r = 0.19, P = 0.020）和单独吸烟者（r = 0.58, P < 0.0001）中，SCN-水平与mpo诱导的硫醇损失之间存在显著正相关。12年全因死亡率数据表明，MPO中位数以上与较高的死亡率显著相关，但MPO中位数以下和SCN-中位数以上与SCN-中位数以下相比，生存率更高。Cox比例风险分析显示，SCN-每增加1 μ M，死亡率显著降低（0.991;P = 0.040）。正如预期的那样，研究对象的年龄是研究对象生存的一个强有力的预测指标。总的来说，这些数据表明MPO低于中位数和SCN高于中位数的受试者有更好的长期生存，并且至少在一些人群中，血浆SCN水平升高可能具有保护作用。
Elevated levels of myeloperoxidase (MPO) are associated with poor cardiovascular outcomes. MPO uses H2O2 to generate oxidants including HOCl and HOSCN, from chloride and thiocyanate (SCN-) ions, respectively. SCN- is the preferred substrate. Elevation of this anion decreases HOCl generation and increases HOSCN formation, a thiol-specific oxidant. Such changes are of potential relevance to people with elevated SCN- levels, such as smokers. In this retrospective study, we examined whether elevated plasma MPO and SCN- levels increased thiol oxidation as a result of increased HOSCN formation, and impacted on long-term survival in 176 subjects (74 non-smokers, 46 smokers, and 56 previous smokers) hospitalized after a first myocardial infarction. Plasma thiols were not significantly altered in smokers compared to non-smokers or past smokers. However, significant positive correlations were detected between SCN- levels and MPO-induced thiol loss in the total population (r = 0.19, P = 0.020) and smokers alone (r = 0.58, P < 0.0001). Twelve-year all-cause mortality data indicate that above median MPO is significantly associated with higher mortality, but below-median MPO and above-median SCN- results in increased survival, compared to below-median SCN-. Cox proportional hazard analysis showed a significant decrease in mortality for each 1 mu M increase in SCN- (0.991; P = 0.040). Subject age was, as expected, a strong predictor of subject survival. Overall these data suggest that subjects with below-median MPO and above-median SCN- have better long-term survival, and that elevated plasma levels of SCN- might be protective in at least some populations.