Activated TGFβ Signaling in the Heart After Myocardial Infarction
We have previously shown that myofibroblasts of the healed 8 week infarct scar overexpress transduction proteins that may be linked to elevated deposition of extracellular matrix components in this tissue. Other work suggests that TGFβ1, may be involved in cardiac fibrosis and myocyte hypertrophy. The significance of the altered TGFβ signaling 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 TGFβ1 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 remnant myocytes) and the infarct scar (nonmyocytes dominated by myofibroblasts). Both TGFβ1 mRNA abundance (Northern analysis) and protein levels (ELISA) were significantly increased in the infarct scar versus control values, and this trend was positively correlated to increased collagen type I expression in this tissues. Cardiac Smad 2, 3, and 4 proteins were significantly increased in border and scar tissues versus control values. Immunofluorescent studies indicated that Smad proteins were proximally localized to cellular nuclei in the infarct scar. TβRI (53 kDa) protein expression was significantly reduced in the scar, while the 75kDa and 110kDa isoforms of TβRII were unchanged and significantly increased respectively, in the infarct scar. These results indicate that TGFβ/Smad signaling may be involved in the remodeling of the infarct scar after the completion of wound healing per se, via ongoing stimulation of matrix deposition.
KeywordsFibril Cardiol Gelatin Ketamine Aldosterone
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