Abstract
Cardiac hypertrophy could be induced by ambient fine particulate matter (PM2.5) exposure. Since cardiac hypertrophy represents an early event leading to heart dysfunction, it is necessary to explore the molecular mechanisms, which are largely unknown. In the present study, an ambient particulate matter exposure mice model was established to explore its adverse effects related to the heart and the potential mechanisms. Forty-eight male C57BL/6 mice were randomly subjected to three groups: filtered air group, unfiltered air group and concentrated air group, and were exposed for 8 and 16 weeks, 6 h/day, respectively. In vitro experiments, the cardiac muscle cell line (HL-1) was treated with PM2.5 (0, 25, 50 and 100 μg/mL) for 24 h. In the present study, cardiac hypertrophy was occurred in vivo and vitro after exposure to PM2.5. Mechanistically, circ_0001859 could sponge miR-29b-3p, which could interact with 3'UTRs of Ctnnb1 (gene name of β-catenin). And Ctnnb1 expression was transcriptionally inhibited by si-circ_0001859 or miR-29b-3p mimic in HL-1 cells. Additionally, miR-29b-3p inhibitor could also make a reversion about the inhibition effect of circ_0001859 silencing on Ctnnb1 mRNA level in HL-1 cells. Functionally, knockout of circ_0001859 or overexpression of miR-29b-3p could inhibit LEF1/IGF-2R pathway and alleviate the progress of hypertrophy induced by PM2.5 in HL-1 cells. And miR-29b-3p inhibitor could reverse the inhibition effect of circ_0001859 silencing on hypertrophic response induced by PM2.5 in HL-1 cells. Consequently, the data demonstrated that circRNA_0001859 promoted the process of cardiac hypertrophy through suppressing miR-29b-3p leading to enhance Ctnnb1 level, and activated downstream pathway molecules LEF1/IGF-2R.