Fenofibrate ameliorates cardiac hypertrophy by activation of peroxisome proliferator-activated receptor-alpha partly via preventing p65-NF kappa B binding to NFATc4

作者：Zou Jian; Le Kang; Xu Suowen; Chen Jianwen; Liu Zhiping; Chao Xiaojuan; Geng Biao; Luo Jiani; Zeng Siyu; Ye Jiantao^*; Liu Peiqing

来源：Molecular and Cellular Endocrinology, 2013, 370(1-2): 103-112.

DOI：10.1016/j.mce.2013.03.006

• Fenofibrate
• Cardiac hypertrophy
• NFATc4
• p65-NF kappa B
• PPAR-alpha

Fenofibrate, a specific peroxisome proliferator-activated receptor alpha (PPAR-alpha) 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-NF kappa B) induced by pressure overload or angiotensinII (AngII). Moreover, fenofibrate increased the association of PPAR-alpha with NFATc4 in nucleus, which inhibited the interaction of NFATc4 with p65-NF kappa B. Our results suggested that the anti-hypertrophic effect of fenofibrate may be partially attributed to activation of PPAR-alpha, which decreases the binding of p65-NF kappa B to NFATc4 and thereby inhibits transactivation of NFATc4.

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