Elevation of expression of Smads 2, 3, and 4, decorin and TGF-beta in 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 elevate d deposition of structural matrix proteins in this tissue. Other work sugge sts that TGF-beta 1 may be involved in cardiac fibrosis and myocyte hypertr ophy, flowerer, the significance of the altered TGF-B signaling in heart fa ilure in the chronic phase of post-myocardial infarction (MI), particularly in the ongoing remodeling of the infarct scar, remains unexplored. Pattern s of cardiac TGF-beta 1 and Smad 2, 3, and 4 protein expression were invest igated 8 weeks after MI and were compared to relative collagen deposition i n border tissues (containing remnent myocytes) and the infarct scar (non-my ocytes). Both TGF-beta 1 mRNA abundance and protein levels were significant ly increased in the infarct scar v control values, and this trend was posit ively correlated to increased collagen type I expression. Cardiac Smad 2, 3 , and 4 proteins were significantly increased in border and scar tissues v control values. Immunofluorescent studies indicated that Smad proteins loca lized 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 sca r v staining patterns of control sections. Expression of T beta RI (53 kDa) protein was significantly reduced in the scar, while the 75 kDa and 110 kD a isoforms of T beta RII were unchanged and significantly increased in scar , respectively. These results indicate that TGF-beta/Smad signaling may be involved in the remodeling of the infarct scar after the completion of woun d healing per se, via ongoing stimulation of matrix deposition. (C) 1999 Ac ademic Press.