RUNX1 facilitates heart failure progression through regulating TGF-β-induced cardiac remodeling.

Abstract

Heart failure is caused by acute or chronic cardiovascular diseases with limited treatments and unclear pathogenesis. Therefore, it is urgent to explore new therapeutic targets and reveal new pathogenesis for heart failure. We carried out heart failure animal model by transverse aortic arch constriction (TAC) in mice. The left ventricular internal diameter diastole (LVIDd), left ventricular internal diameter systole (LVIDs), and ejection fraction (EF) value were detected using ultrasound and myocardial fibrosis was evaluated by Masson stain assay. Cell apoptosis in myocardial tissues were detected by TUNEL immunofluorescence stain. Signal pathway analysis was performed by dual-luciferase reporter assay and western blot. Our results showed that inhibition of RUNX1 led to remission of cardiac enlargement induced by TAC in mice. Inhibition of RUNX1 also caused raise of EF and FS value under TAC-induced condition. Besides, RUNX1 inhibition mice showed decreased myocardial fibrosis area under TAC-induced condition. RUNX1 inhibition caused decrease of apoptotic cell rate in myocardial tissues under TAC. Interestingly, we found that RUNX1 could promote the activation of TGF-β/Smads in dual-luciferase reporter assay. We illustrated that RUNX1 could be considered as a new regulator of myocardial remodeling by activating TGF-β/Smads signaling. Based on this, we concluded that RUNX1 may be developed as a new therapeutic target against heart failure in the future. In addition, this study also provide a new insight for the etiological study on heart failure.