Activating Transcription Factor 3 Protects against Pressure-Overload Heart Failure via the Autophagy Molecule Beclin-1 Pathway

• DOI: 10.1124/mol.113.090092
• Publication Date: 2014-02-19T05:16:16Z
• Authors: Heng Lin; Hsiao-Fen Li; Hsi-Hsien Chen; Pei-Fang Lai; Shu-Hui Juan; Jin-Jer Chen; Ching-Feng Cheng
• Keywords: Activating transcription factor; ATF3; Contractility; CTCF; ATF4; Pressure overload

Activating transcription factor 3 (ATF3), a cAMP response element-binding protein/ATF family factors member, has been implicated in the cardiovascular and inflammatory system is rapidly induced by ischemic-reperfusion injuries. We performed transverse aortic banding (TAB) experiments using ATF3 gene-deleted mice (ATF3^−/−) wild-type (WT) to determine what effect it might have on heart failure pressure overloading. Compared with WT mice, ATF3^−/− were found echocardiography decreased left ventricular contractility loss of normal cardiac hypertrophic remodeling. The had greater numbers terminal deoxynucleotidyl transferase–mediated digoxigenin-deoxyuridine nick-end labeling–positive cells higher levels activated caspase-3, as well more apoptosis. Restoration expression adenovirus-induced treatment significantly improved after TAB. results from molecular biochemical analyses, including chromatin immune-precipitation vitro /in vivo promoter assays, showed that bound ATF/cAMP element Beclin-1 reduced autophagy via suppression Beclin-1–dependent pathway. Furthermore, infusion <i>tert</i>-butylhydroquinone (tBHQ), selective inducer, increased nuclear erythroid 2–related transcriptional factor, inhibited TAB-induced dilatation, contractility, thereby rescuing failure. Our study identified new epigenetic regulation mediated stress-inducible gene dysfunction. These findings suggest activator tBHQ may therapeutic potential for pressure-overload chronic hypertension or other overload mechanisms.