In addition to mediating cell-to-cell electrical coupling, gap junctions are 
important in tissue repair, wound healing, and scar formation. The expression 
and distribution of connexin43 (Cx43), the major gap junction protein expressed 
in the heart, are altered substantially after myocardial infarction (MI); 
however, the effects of Cx43 remodeling on wound healing and the attendant 
ventricular dysfunction are incompletely understood. Cx43-deficient and 
wild-type mice were subjected to proximal ligation of the anterior descending 
coronary artery and followed for 6 days or 4 wk to test the hypothesis that 
reduced expression of Cx43 influences wound healing, fibrosis, and ventricular 
remodeling after MI. We quantified the progression of infarct healing by 
measuring neutrophil expression, collagen content, and myofibroblast expression. 
We found significantly reduced transformation of fibroblasts to myofibroblasts 
at 6 days and significantly reduced collagen deposition both in the infarct at 6 
days and at 4 wk in the noninfarcted region of Cx43-deficient mice. As expected, 
transforming growth factor (TGF)-beta, a profibrotic cytokine, was dramatically 
upregulated in MI hearts, but its phosphorylated comediator (pSmad) was 
significantly downregulated in the nuclei of Cx43-deficient hearts post-MI, 
suggesting that downstream signaling of TGF-beta is diminished substantially in 
Cx43-deficient hearts. This diminution in profibrotic TGF-beta signaling 
resulted in the attenuation of adverse structural remodeling as assessed by 
echocardiography. These findings suggest that efforts to enhance the expression 
of Cx43 to maintain intercellular coupling or reduce susceptibility to 
arrhythmias should be met with caution until the role of Cx43 in infarct healing 
is fully understood.