Early life persistent vitamin D deficiency exacerbates arrhythmias and autonomic imbalance following acrolein exposure in mice.
Citation:
Stratford, K., N. Coates, A. Ledbetter, A. Farraj, AND M. Hazari. Early life persistent vitamin D deficiency exacerbates arrhythmias and autonomic imbalance following acrolein exposure in mice. Annual Meeting of the Society of Toxciology, Baltimore, Maryland, March 12 - 16, 2017.
Impact/Purpose:
This work helps identify potential modifiable factors that influence cardiopulmonary responses to air pollution. The demonstration that nutritional deficiencies influence susceptibility to air pollution may increase our understanding of air pollution health effects in young children and adults in part by potentially uncovering a biologically plausible mechanism for epidemiological findings linking exposure to air pollution to increased cardiovascular morbidity and mortality.
Description:
Epidemiological and animal data have conclusively linked adverse cardiovascular outcomes to air pollution exposure. As such, cardiovascular function is maintained by adequate levels of certain essential micronutrients like vitamin D. Unfortunately, vitamin D deficiency (VDD) has become highly prevalent in the United States, as well as in the world, even affecting otherwise healthy individuals. My initial studies showed that VDD alters cardiac function, increases cardiac arrhythmia and HRV (i.e. indirect measure of autonomic tone) in mice; this response is further exacerbated after smog exposure. VDD has been shown to alter the responsiveness of transient receptor potential A1 (TRPA1) channels, which we have previously shown to be involved in cardiopulmonary dysfunction to acrolein, which is a ubiquitous air pollutant and potent TRPA1 agonist. The effect of VDD on TRPA1-induced air pollution responses is not known and is the purpose of this study. 3-week old mice were placed on a VDD or normal diet (ND) for 19 weeks and then implanted with radiotelemeters for the measurement of heart rate, electrocardiogram and HRV. Mice were exposed to filtered air then acrolein for 3 hours each on separate days. During exposure, ventilatory function and ECG were simultaneously recorded. Acrolein increased parasympathetic tone in ND mice, but not VDD mice during exposure. However, acrolein caused cardiac arrhythmias only in VDD mice during exposure. Similar to previous studies, ventilatory function was altered during acrolein exposure indicating airway irritation in ND mice; this was worsened by VDD. In conclusion, VDD appears to worsen the cardiopulmonary effects of air pollution and TRPA1 could be a potential mediator in the mechanism. (This abstract does not reflect USEPA policy)