Lack of ecto-5′-nucleotidase (CD73) promotes arteriogenesis

Adenosine can stimulate angiogenesis, but its role in the distinct process of arteriogenesis is unknown. We have previously reported that mice lacking ecto-5-nucleotidase (CD73/) show enhanced monocyte adhesion to the endothelium after ischaemia, which is considered to be an important trigger for arteriogenesis. Hindlimb ischaemia was induced in wild-type (WT) and CD73/ mice to study the role of extracellularly formed adenosine in arteriogenesis. Magnetic resonance angiography (MRA) was performed for serial visualization of newly developed vessels at a spatial resolution of 1 nL, and high-energy phosphates (HEP) were quantified by P-31 MR spectroscopy (MRS). MRA of CD73/ mice revealed substantially enhanced collateral artery conductance at day 7 [CD73/: 0.73 0.11 a.u. (arbitrary units); WT: 0.44 0.13 a.u.; P 0.01, n 6], and MRS of the affected hindlimb showed a faster restoration of HEP in correlation with enhanced functional recovery in the mutant. Additionally, histology showed no differences in capillary density between the groups but showed an increased monocyte infiltration in hindlimbs of CD73/ mice. Serial assessment of dynamic changes of vessel growth and metabolism in the process of arteriogenesis demonstrate that the lack of CD73-derived adenosine importantly promotes arteriogenesis but does not alter angiogenesis in our model of hindlimb ischaemia.