SPON2 and heart failure: For example, Spon2 encodes mindin, an extracellular matrix protein highly expressed in cardiac tissue, and plays various roles, including (1) serving as a ligand for integrin during inflammation [37], (2) inhibiting angiogenesis [38], and (3) playing an anti-hypertrophic role, protecting against cardiac remodeling observed in heart failure by attenuating AKT/GSK3β and TGF-β1-Smad signaling [39].