Macrophages have been suggested to be beneficial for myocardial wound healing. 
We investigated the role of macrophages in myocardial wound healing by 
inhibition of macrophage infiltration after myocardial injury. We used a murine 
cryoinjury model to induce left ventricular damage. Infiltrating macrophages 
were depleted during the 1st week after cryoinjury by serial intravenous 
injections of clodronate-containing liposomes. After injury, the presence of 
macrophages, which secreted high levels of transforming growth factor-beta and 
vascular endothelial growth factor-A, led to rapid removal of cell debris and 
replacement by granulation tissue containing inflammatory cells and blood 
vessels, followed by myofibroblast infiltration and collagen deposition. In 
macrophage-depleted hearts, nonresorbed cell debris was still observed 4 weeks 
after injury. Secretion of transforming growth factor-beta and vascular 
endothelial growth factor-A as well as neovascularization, myofibroblast 
infiltration, and collagen deposition decreased. Moreover, macrophage depletion 
resulted in a high mortality rate accompanied by increased left ventricular 
dilatation and wall thinning. In conclusion, infiltrating macrophage depletion 
markedly impairs wound healing and increases remodeling and mortality after 
myocardial injury, identifying the macrophage as a key player in myocardial 
wound healing. Based on these findings, we propose that increasing macrophage 
numbers early after myocardial infarction could be a clinically relevant option 
to promote myocardial wound healing and subsequently to reduce remodeling and 
heart failure.