Elevation of Expression of Smads 2, 3, and 4, Decorin and TGF-βin the Chronic Phase of Myocardial Infarct Scar Healing

We have previously shown that non-myocytes present in healed 8-week infarct scar overexpress transduction proteins required for initiating the elevated deposition of structural matrix proteins in this tissue. Other work suggests that TGF-β1 may be involved in cardiac fibrosis and myocyte hypertrophy. However, the significance of the altered TGF-βsignaling in heart failure in the chronic phase of post-myocardial infarction (MI), particularly in the ongoing remodeling of the infarct scar, remains unexplored. Patterns of cardiac TGF-β1 and Smad 2, 3, and 4 protein expression were investigated 8 weeks after MI and were compared to relative collagen deposition in border tissues (containing remnent myocytes) and the infarct scar (non-myocytes). Both TGF-β1 mRNA abundance and protein levels were significantly increased in the infarct scarvcontrol values, and this trend was positively correlated to increased collagen type I expression. Cardiac Smad 2, 3, and 4 proteins were significantly increased in border and scar tissuesvcontrol values. Immunofluorescent studies indicated that Smad proteins localized proximal to the cellular nuclei present in the infarct scar. Decorin mRNA abundance was elevated in border and infarct scar, and the pattern of decorin immunostaining was markedly altered in remote remnant heart and scarvstaining patterns of control sections. Expression of TβRI (53 kDa) protein was significantly reduced in the scar, while the 75 kDa and 110 kDa isoforms of TβRII were unchanged and significantly increased in scar, respectively. These results indicate that TGF-β/Smad signaling may be involved in the remodeling of the infarct scar after the completion of wound healingper se, via ongoing stimulation of matrix deposition.