Adipocyte Enhancer Binding Protein 1 (AEBP1) inhibition mediates cardiac reverse remodeling by regulating MRTFB and RUNX2 signaling [Cut&Run]

Although Adipocyte enhancer binding protein 1 (AEBP1) and Aortic carboxypeptidase-like protein (ACLP, full-length protein coded by AEBP1) have been implicated in pathological fibrosis across multiple organs including the heart, its functional role in cardiac fibrosis remains unknown.

Here, we demonstrate that AEBP1 is a critical mediator of myocardial fibrosis and adverse cardiac remodeling. Fibroblast-specific knockout or myocardial knockdown of Aebp1 significantly improves cardiac function and prevents pathological remodeling in murine models of myocardial ischemia and pressure-overload induced injury. In human myocardial tissue culture studies, ACLP overexpression induces pathological remodeling in non-failing hearts, whereas AEBP1 knockdown induces structural reverse remodeling in failing myocardium.