Macrophages contribute to vessel normalization during healing of ischemic injury

• Physiological regression of superfluous micro-vessels, vascular pruning, is observed during formation of functional vascular networks in fetal development. The current study investigates the vascular dynamics during healing of injured adult tissues in the mouse model of hind limb ischemia. We found that prompt angiogenesis that occurs in M. gastrocnemius to compensate for loss of tissue perfusion, results in blood vessel densities that are higher than those found in healthy muscles. Vessel density peaked at day 14 post ischemia to thereafter recede to normal levels by day 21, indicating that vessel pruning occurs during healing to ensure establishment of an optimal vascular tree. Macrophages are professional phagocytes and we found them present in high numbers at sites of ischemic injury, where they were positioned in close contact with the vascular network and displayed phagocytic activity at the time of vessel pruning. Interestingly, macrophage depletion between day 14 and 21 post-ischemia resulted in reduced vessel regression. Indeed, by using a reporter mouse for endothelial cells, we found that macrophages engulf endothelial cells at the ischemic site at this time point. Taken together, our results indicate a role for macrophages in vessel normalization by pruning superfluous vasculatur segments that form initially during healing of ischemic injuries. 

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