Effect of Environmentally-derived Sex Steroids on Coxsackievirus B3 Myocarditis: Focus on Vitamin D and Bisphenol A
Embargo until
2020-08-01
Date
2016-07-11
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Johns Hopkins University
Abstract
Myocarditis is an inflammatory heart disease that leads to DCM and heart failure. Sex hormones play a vital role in the development of myocarditis with testosterone driving disease in males. In contrast, estrogen mediates cardioprotection in females. Since myocarditis is influenced by sex hormones, it is highly probable that environmental factors like vitamin D and endocrine disruptors like bisphenol A (BPA) and BPS, which interfere with natural hormone signaling, could play a part in the progression of the disease. To our knowledge no one has examined the role of vitamin D receptor or endocrine disruptors like BPA on myocarditis. In order to examine the role of vitamin D on viral myocarditis, we examined vitamin D receptor knockout mice fed a calcium-supplemented diet to prevent rickets. For BPA and BPS experiments, we exposed mice to various doses of endocrine disruptors dissolved in their drinking water for two weeks and then examined their effect on viral myocarditis. We found that vitamin D receptor signaling protects female mice from myocarditis, but increases myocarditis in males. For endocrine disruptor exposure we found that BPA and BPS were each able to increase viral myocarditis by increasing mast cell numbers/ degranulation and T cells in female BALB/c mice. BPA exposure was also found to increase viral myocarditis in male BALB/c mice. In contrast, BPA exposure had no significant effect on myocarditis in female C57BL/6 mice. Surprisingly, housing mice in plastic cages was able to cause mast cell activation in females and increase myocarditis in male BALB/c mice. These data indicate that the traditional cages that investigators use to house their mice may be altering the immune response in a sex-specific manner. Our data show that exposure to endocrine disruptors significantly alter the immune response according to sex and mouse strain.
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Keywords
myocarditis, endocrine disruptors, bisphenol A, BPA, bisphenol S, BPS, vitamin D, vitamin D receptor, VDR, mast cells, plastics, animal caging