Adipocyte Enhancer Binding Protein 1 (AEBP1) Inhibition as a Potential Anti-Fibrotic Therapy in Heart Failure.

Abstract Persistent activation of fibroblasts to myofibroblasts leads to increased myocardial fibrosis which is often detrimental to cardiac function and leads to heart failure (HF). Adipocyte enhancer binding protein (AEBP1) plays a crucial role in fibroblast activation following injury in the kidney, liver, and lungs. AEBP1 inhibition resulted in fibrosis attenuation in these organs. AEBP1 has been reported to be upregulated in the HF myocardium, however, its role in cardiac fibrosis progression is not well understood. In this study, we show that AEBP1 is crucial for cardiac fibroblast activation and AEBP1 inhibition prevents cardiac fibroblast differentiation in vitro. AEBP1 knock-down (KD) in mouse models of acute cardiac fibrosis improved cardiac structure and function. Tissue culture studies of non-failing donor myocardium resulted in increased cellular hypertrophy and tissue remodeling following AEBP1 overexpression. Contrarily, a significant improvement in cardiac structure evident from reduced cardiomyocyte hypertrophy and reduced fibrosis was observed in chronic HF myocardium following AEBP1 KD. Overall, we show that AEBP1 plays a critical role in fibrogenesis, and its inhibition has the potential to attenuate fibrosis in acute and chronic HF.