Effects of PPARαactivation on AngⅡ-induced cardiomyocyte hypertro-phy and interaction of NFATc4 with p65-NFκB / 中国病理生理杂志

ABSTRACT

AIM: To investigate the effects of fenofibrate on angiotensin Ⅱ ( AngⅡ)-induced cardiomyocyte hypertrophy .METHODS:Primary neonatal cardiomyocytes were pretreated with fenofibrate (10μmol/L) for 1 h followed by stimulation with AngⅡ(100 nmol/L).The mRNA levels of ANF, BNP andβ-MHC were measured by real-time PCR. Western blotting was employed to determine the nuclear translocations of NFATc 4 and p65-NFκB.Co-immunoprecipitation was used to investigate the interaction of NFATc 4 with p65-NFκB in the nucleus of cardiomyocytes .In addition, the DNA binding activity of NFATc4 on the BNP promoter was determined by EMSA .RESULTS:Fenofibrate significantly inhibited AngⅡ-induced cardiomyocyte hypertrophy .Fenofibrate treatment inhibited the nuclear translocations of NFATc 4 and p65-NFκB, as well as the interactions of NFATc 4 with p65-NFκB in the nucleus of cardiomyocytes induced by AngⅡ.Fenofi-brate inhibited the binding activity of NFATc 4 with the BNP promoter , which was strengthened by AngⅡ.CONCLU-SIONFenofibrate enhances the interaction of NFATc 4 with PPARα, decreases the interaction of NFATc 4 with p65-NFκB in the nucleus of cardiomyocytes , and inhibits the DNA binding activity of NFATc 4 induced by AngⅡ, which may be the important mechanisms of fenofibrate on inhibiting cardiac hypertrophy .