Fenofibrate ameliorates cardiac hypertrophy by activation of peroxisome proliferator-activated receptor-α partly via preventing p65-NFκB binding to NFATc4.

Fenofibrate, a specific peroxisome proliferator-activated receptor alpha (PPAR-α) agonist, was reported to inhibit cardiac hypertrophy. However, the detailed molecular mechanisms and particularly the transcriptional components that are decisive in this process remain to be elucidated. Here we found that fenofibrate ameliorated cardiac hypertrophy in vitro and in vivo. Fenofibrate prevented nuclear translocation of nuclear factor of activated T-cells c4 (NFATc4) and p65 subunit of nuclear factor-kappa B (p65-NFκB) induced by pressure overload or angiotensinII (AngII). Moreover, fenofibrate increased the association of PPAR-α with NFATc4 in nucleus, which inhibited the interaction of NFATc4 with p65-NFκB. Our results suggested that the anti-hypertrophic effect of fenofibrate may be partially attributed to activation of PPAR-α, which decreases the binding of p65-NFκB to NFATc4 and thereby inhibits transactivation of NFATc4.