High plasma thiocyanate levels are associated with enhanced myeloperoxidase-induced thiol oxidation and long-term survival in subjects following a first myocardial infarction

P E Nedoboy, P E Morgan, T J Mocatta, A M Richards, C C Winterbourn, Michael Jonathan Davies

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

33 Citationer (Scopus)

Abstract

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 μM 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.

OriginalsprogEngelsk
TidsskriftFree Radical Research
Vol/bind48
Udgave nummer10
Sider (fra-til)1256-66
Antal sider11
ISSN1071-5762
DOI
StatusUdgivet - okt. 2014

Citationsformater