Short-term effects of ambient gaseous air pollution on blood platelet mitochondrial DNA methylation and myocardial ischemia

Abstract

Background: The potential effects of short-term exposure to major ambient gaseous pollutants (ozone: O₃, carbon monoxide: CO, and sulfur dioxide: SO₂) on platelet mitochondrial DNA (mtDNA) methylation have been uncertain and no studies have examined whether platelet mtDNA methylation levels could modify the associations between ambient gaseous pollutants and the risks of ST-segment depression (STDE) and T-wave inversion events (TIE), two indicators of myocardial ischemia.

Methods: This study used data from a randomized, double-blind, placebo-controlled intervention study with a standardized 24-hour exposure protocol among 110 participants in Beijing. Absolute changes in platelet mtDNA methylation (ACmtDNAm) levels were determined by two repeated measurements on platelet mtDNA methylation levels in blood samples collected before and after the 24-hour exposure period. A multivariable linear regression model and a generalized linear model with a Poisson link function were used to investigate the associations of ambient gaseous pollutants with platelet mtDNA methylation levels, STDE, and TIE, respectively.

Results: Short-term O₃ exposure was significantly associated with decreased ACmtDNAm at ATP6_P1 but increased ACmtDNAm at mt12sRNA, MT-COX1, and MT-COX1_P2; short-term CO and SO₂ exposures were significantly associated with decreased ACmtDNAm at D-loop, MT-COX3- and ATP-related genes. Moreover, short-term O₃ exposure was significantly associated with increased risks of STDE and TIE, and ACmtDNAm at MT-COX1 and MT-COX1_P2 modified the association between short-term O₃ exposure and STDE events. L-Arg supplementation attenuated the effects of ambient gaseous pollutants, particularly O₃, on ACmtDNAm and STDE.

Conclusions: Platelet mtDNA methylation levels are promising biomarkers of short-term exposure to ambient gaseous air pollution, and are likely implicated in the mechanism behind the association of ambient O₃ pollution with adverse cardiovascular effects. L-Arg supplementation showed the potential to mitigate the adverse effects of ambient O₃ pollution.

Keywords: Gaseous pollutants; Methylation; Myocardial ischemia; Platelet mitochondrial DNA; ST-segment depression.