Bisphenol A (BPA) exacerbates acute myocarditis in female BALB/c by activating mast cells and the inflammasome (HUM1P.302)

Abstract

Abstract Myocarditis is an inflammatory heart disease that is the leading cause of heart failure in young adults. Sex hormones play a vital role in development of myocarditis with testosterone driving disease in males. Whereas, estrogen, via Estrogen Receptor α (ERα) mediates cardioprotection in females. Since myocarditis is influenced by sex hormones, it is highly probable that endocrine disruptors (EDs); which interfere with natural hormones, will play a part in the progression of the disease. The human population is exposed to Bisphenol A (BPA), a known ED that binds the ER, from plastics, such as water bottles and plastic food containers. BPA has been found to act through ERβ in cardiomyoctes to increase cardiac arrhythmias. Thus, BPA could increase myocarditis through deleterious actions of the ERβ rather than beneficial effects via ERα. To our knowledge no one has examined the role of EDs like BPA on myocarditis. We found that clinically relevant doses (25 µg/L and 250 µg/L) of BPA increased acute myocarditis compared to control water. We found BPA significantly decreased ERα, while ERβ was significantly increased. We found that mast cells (cKit) are largely responsible for the increase in inflammation along with CD4 Thelper cells. IL-1β, IFN-γ, TLR4, Caspase-1, Mmp9, and ST2 were all increased with BPA treatment which all lead to increased inflammation and disease. We believe that BPA is influencing the inflammasome and mast cells leading to exacerbation of disease in females.