In contrast, cardiomyocyte-specific loss of Smad3 attenuated remodeling and reduced cardiomyocyte apoptosis, which was associated with decreased NOX-2, nitrosative stress, and matrix metalloproteinase 2 (MMP-2) levels in the myocardium.223 In a cardiac hypertrophy model induced by pressure overload, however, Smad3 deletion worsened cardiac hypertrophy and survival after TAC surgery, although it did reduce cardiac fibrosis.224 Myofibroblast-specific Smad3-knockout mice also showed unexpectedly exacerbated systolic dysfunction after TAC surgery. This evidence concerns the gene MMP2 and persistent truncus arteriosus.