Ambient Particulate Matter and Acrolein Co-Exposure Increases Myocardial Dyssynchrony in Mice: Evidence for TRPA1 Involvement
Citation:
Thompson, L., L. Walsh, B. Martin, J. Mcgee, C. Wood, K. Kovalcik, P. Pancras, N. Coates, A. Ledbetter, D. Davies, W. Cascio, M. Higuchi, M. Hazari, AND A. Farraj. Ambient Particulate Matter and Acrolein Co-Exposure Increases Myocardial Dyssynchrony in Mice: Evidence for TRPA1 Involvement. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 167(2):559-572, (2019). https://doi.org/10.1093/toxsci/kfy262
Impact/Purpose:
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. The presence of unique co-pollutant effects even at low exposure concentrations suggest that the effects of exposure to air pollution mixtures may not be accurately predicted by ambient levels of single pollutants, and may in fact be underestimated. The mediation of effects by a biologically relevant mechanism strengthens the findings pointing to the potential for synergistic effects.
Description:
Air pollution is a complex mixture of particulates, gases, and aldehydes. As such, attributing health effects to specific air pollutants in a given ambient air shed and identifying plausible biological mechanisms can be difficult when pollutants are studied in isolation. Here, we examined the potential for interactive cardiovascular effects of repeated, intermittent co-exposure to concentrated ambient particulate matter (CAPs) and acrolein, and the potential role of transient receptor potential cation channel A1 (TRPA1), which we previously linked to air pollution-induced cardiac arrhythmogenesis. Female B6129 mice and Trpa1-/- mice (n=6) were exposed to filtered air (FA), CAPs (46 µg/m3 of PM2.5 approximately 150 nm diameter), Acrolein (0.42 ppm) or CAPs+Acrolein for 3hrs/day, 2days/week, for 4 weeks. Cardiac strain data, heart function and dimensions, and transmitral blood flow were investigated with echocardiography (40 MHz) before exposures, 1 day after the first exposure, and 1 day after the final exposure. Elapsed time between peak strain in adjacent wall segments (i.e. myocardial strain delay), a measure of myocardial dyssynchrony, increased by ~5-fold in B6129 mice after the final exposure to CAPs+Acrolein when compared to strain delay in B6129 mice exposed to FA, CAPs, or Acrolein alone, and when compared to strain delay in Trpa1-/- mice exposed to CAPs+Acrolein. There were no changes after the first exposure in any group. This study provides evidence that particulate matter may interact with co-pollutants like acrolein to produce greater than additive health effects via TRPA1, particularly after repeated low-level exposure.
URLs/Downloads:
DOI: Ambient Particulate Matter and Acrolein Co-Exposure Increases Myocardial Dyssynchrony in Mice: Evidence for TRPA1 Involvement