Ambient Particulate Matter and Acrolein Co-Exposure Increases Myocardial Dyssynchrony in Mice via TRPA1

Toxicol Sci. 2019 Feb 1;167(2):559-572. doi: 10.1093/toxsci/kfy262.

Abstract

Air pollution is a complex mixture of particulate matter and gases linked to adverse clinical outcomes. As such, studying responses to individual pollutants does not account for the potential biological responses resulting from the interaction of various constituents within an ambient air shed. We previously reported that exposure to high levels of the gaseous pollutant acrolein perturbs myocardial synchrony. Here, we examined the effects of repeated, intermittent co-exposure to low levels of concentrated ambient particulates (CAPs) and acrolein on myocardial synchrony and the role of transient receptor potential cation channel A1 (TRPA1), which we previously linked to air pollution-induced sensitization to triggered cardiac arrhythmia. Female B6129 and Trpa1-/- mice (n = 6/group) were exposed to filtered air (FA), CAPs (46 µg/m3 of PM2.5), Acrolein (0.42 ppm), or CAPs+Acrolein for 3 h/day, 2 days/week for 4 weeks. Cardiac ultrasound was conducted to assess cardiac synchronicity and function before and after the first exposure and after the final exposure. Heart rate variability (HRV), an indicator of autonomic tone, was assessed after the final exposure. Strain delay (time between peak strain in adjacent cardiac wall segments), an index of myocardial dyssynchrony, increased by 5-fold after the final CAPs+Acrolein exposure in B6129 mice compared with FA, CAPs, or Acrolein-exposed B6129 mice, and CAPs+Acrolein-exposed Trpa1-/- mice. Only exposure to acrolein alone increased the HRV high frequency domain (5-fold) in B6129 mice, but not in Trpa1-/- mice. Thus, repeated inhalation of pollutant mixtures may increase risk for cardiac responses compared with single or multiple exposures to individual pollutants through TRPA1 activation.

MeSH terms

  • Acrolein / toxicity*
  • Air Pollutants / toxicity*
  • Animals
  • Arrhythmias, Cardiac / chemically induced*
  • Arrhythmias, Cardiac / metabolism
  • Drug Synergism
  • Female
  • Heart Rate / drug effects
  • Inhalation Exposure / adverse effects*
  • Mice
  • Mice, Knockout
  • Myocardium / metabolism*
  • Particulate Matter / toxicity*
  • TRPA1 Cation Channel / genetics
  • TRPA1 Cation Channel / metabolism*

Substances

  • Air Pollutants
  • Particulate Matter
  • TRPA1 Cation Channel
  • Trpa1 protein, mouse
  • Acrolein