Figure 9: Proposed mechanism underlying ANGPTL2 activity in heart.

Pathologic stimuli increase cardiomyocyte ANGPTL2 expression through Calcineurin-NFAT signalling. Cardiac ANGPTL2 activity causes pathological remodeling by down-regulating AKT-SERCA2A signalling, promoting cardiac dysfunction and decreasing cardiac energy metabolism via PGC-1α and PPAR-α down-regulation. Such pathological remodeling facilitates the transition to HF.