Interactive effects of short-term ozone exposure and plasma biomarkers related to nitric oxide pathway and inflammation on myocardial ischemia

Background: No study has explored the possible interactive effects of short-term ozone (O3) exposure and plasma endothelial and inflammatory biomarkers, including cyclic guanosine monophosphate (cGMP), nitric oxide metabolite (NOx), myeloperoxidase (MPO), and high-sensitive C-reactive protein (hs-CRP), on myocardial ischemia, indicated by ST-segment depression events (STDE) recorded in ambulatory electrocardiograms. Methods: A L-arginine (L-Arg) intervention study with 118 participants was carried out using a standardized 24-h exposure protocol, employing a multivariable linear regression model to assess the effects of O3 exposure on plasma biomarkers, and a generalized linear model to investigate the effects on 24-hour STDE. The possible interactive effects of short-term O3 exposure and plasma biomarkers on indicators of myocardial ischemia were also investigated by including product interaction terms between ambient O3 and plasma biomarkers in the models. We also explored whether L-Arg supplementation could alleviate the adverse effects of ambient O3 exposure. Results: Data from 107 participants were included in final analysis. Short-term O3 exposure was associated with significantly decreased plasma cGMP and MPO levels, and increased 24-h STDE risk, with plasma cGMP and MPO modifying the O3-STDE associations. Participants with lower plasma levels of cGMP or higher MPO demonstrated increased vulnerability to the harmful effects of ambient O3 on 24-h STDE in inferior leads. L-Arg supplementation attenuated the effects of short-term O3 exposure on plasma MPO and hs-CRP. Conclusions: Plasma biomarkers (cGMP and MPO) are likely involved in the potential pathways connecting ambient O3 exposure and harmful cardiac effects. Supplementation with L-Arg showed the potential to mitigate the inverse effects of ambient O3 exposure on inflammation.