Whereas, cardiomyocyte-specific deletion of Smad3, a pivotal downstream effector in the TGF-β1 pathway, protects them from apoptosis in MI and restricts adverse remodeling, fibroblast-specific deletion leads to their hyperproliferation with a concomitant reduction of collagen synthesis leading to post-MI cardiac rupture (174). This evidence concerns the gene SMAD3 and myocardial infarction.