In the present studies, the protein expressions of apoptosis (i.e., cleaved caspase 3 and cleaved PARP), fibrosis (p-Smad3 and TGF-ß), DNA-damage marker (γ-H2AX) and pressure-overload/heart failure biomarkers (ß-MHC/BNP), as well as the cellular levels of fibrotic/collagen-deposition areas in LV myocardium, were significantly and progressively increased from groups 1 to 3. Here, SMAD3 is linked to heart failure.