Objective: 

Monocytes play a crucial role in the process of arteriogenesis, the transformation of pre-existing arterioles into functional arteries. As the AMP-activated protein kinase (AMPK) is implicated in arteriogenesis and angiogenesis as well as inflammation, the relevance of AMPK in monocytes and endothelial cells for vascularisation was analyzed in this study.

Methods and results: 

Recovery of hindlimb blood flow after femoral artery ligation in mice with global AMPKa2 (AMPKa2^-/-) deletion was significantly impaired compared to their wild-type littermates. Part of this effect was attributed to an endothelial defect as vascular repair was also impaired in mice lacking the AMPKa2 in endothelial cells (Tie2-AMPKa2^-/-). Deletion of the AMPKa2 in myeloid cells (LysM-AMPKa2^-/-) abolished the ischemia-induced revasularisation. The identity of subpopulations of immune cells in the stromal vascular fractions (SVF) of subcutaneously implanted Matrigel plugs from AMPKa2^-/- and wild-type mice were analysed by FACs. The numbers of plasmacytoid dentritic cells as well as natural killer cells were increased in the AMPKa2^-/- mice. Analysis of M1 (IL-1b, TNF-a and iNOS) and M2 (FIZZ-1, arginase and YM-1) macrophage polarization markers showed that the expression of FIZZ-1 (found in inflammatory zone-1, M2 marker) was significantly increased in the SVF isolated from Matrigel plugs of the AMPKa2^-/- mice.

Conclusion: 

The deletion of AMPKa2 in the myeloid cell linage completely inhibits vascular repair in the ischemic hindlimb. The observed change in immune cell populations in neovascularized tissue possibly alters the interactions between the different populations of immune cells with severe consequences for reperfusion.