Glutathione-S-Transferase M1, Obesity, Statins, and Autonomic Effects of Particles

Abstract

Rationale: Air pollution by particulate matter (PM) has been associated with cardiovascular deaths, although the mechanism of action is unclear. One proposed pathway is through disturbances of the autonomic control of the heart. Objectives: We tested the hypothesis that such disturbances are mediated by PM increasing oxidative stress by examining the association between PM and the high-frequency (HF) component of heart rate variability as modified by the presence or absence of the allele for glutathione-S-transferase M1 (GSTM1) and the use of statins, obesity, high neutrophil counts, higher blood pressure, and older age. Methods: We examined the association between particles less than 2.5 M in aerodiameter (PM 2.5 ) and HF in 497 participants in the Normative Aging Study, using linear regression controlling for covariates. Main Results: A 10-g/m 3 increase in PM 2.5 during the 48 h before HF measurement was associated with a 34% decrease in HF, 95% confidence interval (Ϫ9%, Ϫ52%), in subjects without the allele, but had no effect in subjects with GSTM1 present. Among GSTM1-null subjects, the use of statins eliminated the effect of PM 2.5 . Obesity and high neutrophil counts also worsened the PM effects with or without GSTM1. Conclusion: The effects of PM 2.5 on HF appear to be mediated by reactive oxygen species. This may be a key pathway for the adverse effects of combustion particles.Keywords: genetic polymorphisms; heart rate variability; oxidative stress; particles A large body of evidence has demonstrated that particulate air pollution (PM) is associated with short-term changes in the risk of death (1-6). An early study showed the risk of dead-on-arrival deaths associated with particles was three times that for all deaths (7). This suggests a predominant effect on sudden deaths from arrhythmias and myocardial infarctions. Subsequent studies have confirmed that PM is associated with myocardial infarctions (8, 9),

Air pollution, oxidative stress and dietary supplementation: a review

“…As observed in the case of cigarette smoke, a significant source of oxidative stress, air pollutants would lower antioxidant defences, with deleterious health consequences [116,117]. Evidence of the potential beneficial effect of antioxidants can be found in studies of elderly subjects in which treatment with statins [108] and n-3 PUFA supplementation [106] had a beneficial effect on response to particulate exposure.…”

“…In a randomised trial conducted in nursing home residents, supplementation with 2 g?day -1 of fish oil (each 1 g capsule contained 83.2 % of omega-3 fatty acids) significantly decreased the effect of PM2.5 on time and frequency domain parameters of HRV [106] This is one of two studies providing evidence that oxidant stress is one of the mechanisms explaining the effect of particle air pollution on the cardiovascular system [107]. The other study reported that statins had a mitigating effect on the HRV effects of particulate air pollution in subjects genetically susceptible to oxidative stress (lacking the GSTM1 allele) [108].…”

“…In particular, subjects with asthma [29], chronic obstructive lung diseases [113], diabetes [114] and cardiovascular diseases [115] have all been shown to have antioxidant deficiency [13] and be more susceptible to the effects of air pollution [108,115]. As observed in the case of cigarette smoke, a significant source of oxidative stress, air pollutants would lower antioxidant defences, with deleterious health consequences [116,117].…”

“…Allergen sensitive subjects with low responsive genotypes show enhanced susceptibility to the adjuvant effects of DEP [126]. A GSTM1 polymorphism has also been shown to increase sensitivity to PM, as evidenced by greater changes in HRV [108]. Moreover, glutaryl coenzyme A inhibitors, i.e.…”

“…Moreover, glutaryl coenzyme A inhibitors, i.e. statins, with known antioxidant and antiinflammatory properties mitigate against the effects of ambient particles on HRV in subjects lacking the GSTM1 allele [107,108].…”