Citation:

Stratford, K., N. Coates, A. Ledbetter, A. Farraj, AND M. Hazari. Acrolein-induced arrhythmias and autonomic imbalance due to early life persistent vitamin D deficiency in mice is mediated by the putative anti-aging factor klotho. Society of Toxicology, San Antonio, Texas, March 11 - 16, 2018.

Impact/Purpose:

These findings may help provide biological plausibility for the epidemiologic studies that link exposure to air pollution to adverse health effects, particularly in susceptible subgroups.

Description:

Although epidemiological, human and animal data have conclusively linked air pollution exposure to adverse cardiovascular outcomes, the severity of responses depends on a number of intrinsic (diet, underlying disease, etc) and extrinsic (e.g. co-stressors) factors. 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. We previously showed that VDD worsens cardiac arrhythmias and causes autonomic imbalance in mice exposed to acrolein, which is a ubiquitous gaseous air pollutant. A number of studies suggest that vitamin D exerts its effects in the body through a putative anti-aging protein called klotho, which is reduced in VDD. Thus, the purpose of this study was to determine whether klotho treatment would ameliorate the acrolein-induced effects due to VDD. We hypothesized that klotho would decrease arrhythmogenesis and autonomic imbalance during acrolein exposure. Three-week old mice were placed on a VDD or normal diet (ND) for 19 weeks and treated with 1 mg/ml klotho (ip) every other day for a month starting at 18 weeks of age. Mice were implanted with radiotelemeters for the measurement of heart rate (HR), electrocardiogram and heart rate variability (HRV). Mice were exposed to filtered air (sham) and then acrolein for 3 hours each on separate days. HR and HRV were significantly decreased during acrolein exposure in VDD mice when compared to ND; this response was blocked by klotho treatment. Although arrhythmias were observed in VDD mice treated with klotho during exposure, there was no difference from ND. Acrolein exposure also caused a significant decrease in tidal volume and increase in ventilatory timing (i.e. airway irritation) in VDD mice which was blocked by klotho. In conclusion, VDD appears to modify the cardiopulmonary response to air pollution through a mechanism involving klotho. Although additional studies are needed to verify these findings, these data suggest klotho treatment could potentially lessen the effects of air pollution in people with VDD. (This abstract does not reflect USEPA policy)

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