Hexabromocyclododecane (HBCD) is one of the most widely used brominated
flame retardants. Although studies have reported that HBCD can cause a wide range of toxic effects on animals including humans, limited information can be found about its
cardiac toxicity. In the present study, zebrafish embryos were exposed to HBCD at low concentrations of 0, 2, 20 and 200 nM. The results showed that HBCD exposure could induce
cardiac hypertrophy and increased deposition of
collagen. In addition, disordered
calcium (Ca(2+)) handling was observed in H9C2 rat cardiomyocyte cells exposed to HBCD. Using small
RNA sequencing and real-time quantitative PCR, HBCD exposure was shown to induce significant changes in the
miRNA expression profile associated with the cardiovascular system. Further findings indicated that miR-1, which was depressed by Nkx2.5, might play a fundamental role in mediating
cardiac hypertrophy and
arrhythmia via its target genes Mef2a and Irx5 after HBCD treatment. HBCD exposure induced an arrhythmogenic disorder, which was triggered by the imbalance of
Ryr2, Serca2a and Ncx1 expression, inducing Ca(2+) overload in the sarcoplasmic reticulum and high Ca(2+)-
ATPase activities in the H9C2 cells.