Citation:

Thompson, L., L. Walsh, N. Coates, A. Ledbetter, D. Davies, M. Higuchi, W. Cascio, M. Hazari, AND A. Farraj. Co-exposure to inhaled ambient particulate matter and acrolein alters myocardial synchrony in mice: evidence for TRPA1 involvement. Society of Toxicology Meeting, New Orleans, LA, March 13 - 17, 2016.

Impact/Purpose:

This work helps disentangle the complexity of air pollution mixtures at ambient air sheds, potential synergistic effects, and mechanisms by which such effects may take place. The elicitation of greater than additive effects with co-exposure to two key air pollutants (i.e. ambient particulate matter and acrolein) provides evidence for synergism between constituents within a mixture and thereby may potentially provide guidance towards a mixtures or multi-pollutant approach to standard setting. These findings also provide biological plausibility to the epidemiological evidence linking exposure to air pollution to increased cardiovascular morbidity and mortality by demonstrating altered function with co-exposure and by linking health effects to a mechanism (i.e. TRPA1) relevant to humans.

Description:

Because air pollution is a complex mixture of constituents, often including particulates and aldehydes, attributing health effects to air pollutants in a given ambient air shed can be difficult when pollutants are studied in isolation. The purpose of this study was to examine the cardiovascular effects of repeated, intermittent co-exposure to concentrated ambient particulate matter (CAPs) and acrolein. We hypothesized that co-exposure would cause greater deficits in myocardial synchrony and performance than exposure to either pollutant alone, and that such effects would be mediated by activation of the transient receptor potential cation channel (TRPA1), a mechanism we previously linked to diesel exhaust-induced increases in cardiac arrhythmogenesis. Female B6129 (WT) mice and Trpa1-/- mice (n=6) were exposed to filtered air (FA), CAPs (~45 µg/m3 of PM2.5 approx. 150 nm diameter), acrolein (0.42 ppm) or CAPs+acrolein for 3 hours a day, 2 days a week, for 4 weeks. Cardiac dimensions, strain data, and mechanical function were investigated with echocardiography (at 40 MHz) before the onset of exposures, 1 day after the first exposure, and 1 day after the final exposure. Preliminary results from after the final exposure indicate that CAPs+acrolein increased myocardial strain delay (indicator of cardiac dyssynchrony) in WT mice by ~5-fold when compared to delay in WT mice exposed to FA, CAPs, or acrolein alone; and when compared to delay in Trpa1-/- mice exposed to CAPs+acrolein. There were no significant differences in strain delay between WT mice exposed to FA, CAPs, or acrolein alone and the corresponding exposure groups in Trpa1-/- mice. Indicators of myocardial performance were not different between groups at the final time-point. These results demonstrate 1) greater than additive cardiac effects of CAPs and acrolein co-exposure and 2) TRPA1 involvement in the loss of cardiac synchrony induced by CAPs and acrolein co-exposure. (This abstract does not reflect EPA policy).

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