Characteristics of Bisphenol Cardiotoxicity: Impaired Excitability, Contractility, and Relaxation

Abstract

Bisphenol a (BPA) is a high production volume chemical that is frequently used to manufacture epoxy resins and polycarbonate plastics. BPA-containing products are now pervasive, and as a result, biomonitoring studies report widespread exposure in > 90% of adults, adolescents, and children. Both epidemiological and experimental studies have reported associations between BPA exposure and adverse cardiovascular health outcomes. With increasing concerns regarding BPA exposure, a few structurally similar bisphenol chemicals have been introduced as replacements, including bisphenol s (BPS) and bisphenol f (BPF). In accordance with the recently established "Key characteristics of cardiovascular toxicants", we reviewed the literature to highlight the immediate effects of bisphenol chemicals on (1) cardiac excitability, and (2) contractility and relaxation. BPA inhibits key cardiac ion channels, impairs cardiac excitability, and acts as a more potent inhibitor as compared to BPF and BPS. Through the inhibition of calcium current, some studies report that bisphenol chemicals can act as negative inotropic agents. Yet, others suggest that low dose exposures may increase contractility and precipitate triggered arrhythmias via the phosphorylation of key calcium handling proteins. Accordingly, we propose additional considerations for future work to comprehensively address the cardiac safety profile of BPA, as compared to replacement chemicals.

Keywords: Bisphenol; Cardiotoxicity; Contractility; Excitability; Relaxation.

Fig. 1

Summary of BPA’s effects on cardiac physiology. Top: effects of BPA on ion channels and intracellular signaling. Bottom: phenotypic effects of BPA on cardiac electrophysiology, intracellular calcium handling, or contraction. Key: ↑ increases, enhances, lengthens; ↓ decreases, blocks, slows, reduces; ∩ non-monotonic dose response; *contradictory results. AP action potential, AV atrioventricular, CaT calcium transient, CV conduction velocity, PLB phospholamban, RYR ryanodine receptor, SERCA SR ATPase. Created with BioRender.com