Abstract 224: 4-phenylbutyric Protects The Heart From Heart Failure, Cardiac Rupture And Remodeling By Alleviating Cardiac Apoptosis And Fibrosis In A Mouse Model Of Myocardial Infaction

Evidences showed that endoplasmic reticulum (ER) stress has involved in cardiac hypertrophy and inhibition of ER stress exerts an effective cardioprotective effect. But little is known about the effect of ER stress inhibition on myocardial infarction (MI). The aim of this study is to investigate whether direct inhibition of ER stress by 4-phenylbutyric acid (4-PBA), an ER stress chemical chaperone, could attenuate MI induced by left coronary artery (LCA) ligation in male C57BL/6 mice. Either NaCl or 4-PBA (20 mg/kg/d) alone was intra-peritoneal injected to the mice immediately after MI for 4 weeks. Heart failure, cardiac rupture and remodeling occurred after MI. There was 52.5% vs 24% death rate in control group vs 4-PBA group during the early phase after MI (2-7 days). The survivals underwent cardiac remodeling with impaired systolic and diastolic functions at the end. The ventricular aneurysm and fibrosis were much smaller in 4-PBA group and the heart functions were improved. Western blot showed that the ER stress markers, Bax, Caspase 3, TGFβ1 and Smad 2/3 in the heart tissues of the control group were significantly increased after MI, in which Bax and Caspase 3 were increased markedly in the early phase of MI, while TGFβ1 and Smad 2/3 were increased obviously in the late phase. 4-PBA decreased those protein levels in the early and late phases of MI respectively. These findings indicate that inhibition of ER stress using 4-PBA could be an effective therapeutic agent protects the heart from post-infarcted heart failure, cardiac rupture and remodeling.