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

Abstract

Background 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. Methods 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. Results 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. Interpretation 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.

The role of IFI16 in regulating PANoptosis and implication in heart diseases

“… [ 129 ] Apoptosis in HF is predominantly driven by factors like oxidants, excessive nitric oxide, angiotensin II, and catecholamines, which trigger caspase activation leading to cardiomyocyte death, a key aspect in the progression of HF. [ 130 ] necroptosis The study found that RIPK1-independent necroptosis contributes to the pathogenesis of DIC, and treatment with rapamycin significantly improves heart function in DIC by reducing MLKL activity and preventing necroptosis. [ 131 ] This paper discusses the mechanisms of cell death, including apoptosis, necrosis, and autophagy.…”

“…The heart’s response to damage and stress is known as cardiac remodeling, and it involves structural alterations, myocardial cell enlargement, and an increase in apoptosis. The remodeling process is intimately associated with the advancement of HF, as the heart’s capacity to contract efficiently and sustain sufficient blood circulation is compromised by the death of cardiomyocytes [ 130 ]. According to recent studies, HF symptoms and cell preservation may benefit from caspase inhibitor-induced apoptosis inhibition, both in vivo and in vitro.…”