Impact of and Mouse Strain Differences on Ischemia-Induced Postnatal Angiogenesis and the Associated Leukocyte Infiltration in a Murine Hindlimb Model of Ischemia.

Strain-related differences in arteriogenesis in inbred mouse strains have already been studied excessively. However, these analyses missed evaluating the mouse strain-related differences in ischemia-induced angiogenic capacities. With the present study, we wanted to shed light on the different angiogenic potentials and the associated leukocyte infiltration of and mice to facilitate the comparison of angiogenesis-related analyses between these strains. For the induction of angiogenesis, we ligated the femoral artery in 8-12-week-old male and mice and performed (immuno-) histological analyses on the ischemic gastrocnemius muscles collected 24 h or 7 days after ligation. As evidenced by hematoxylin and eosin staining, mice showed reduced tissue damage but displayed an increased capillary-to-muscle fiber ratio and an elevated number of proliferating capillaries (CD31/BrdU cells) compared to mice, thus showing improved angiogenesis. Regarding the associated leukocyte infiltration, we found increased numbers of neutrophils (MPO cells), NETs (MPO/CitH3/DAPI), and macrophages (CD68 cells) in mice, whereas macrophage polarization (MRC1 vs. MRC1) and total leukocyte infiltration (CD45 cells) did not differ between the mouse strains. In summary, we show increased ischemia-induced angiogenic capacities in mice compared to mice, with the latter showing aggravated tissue damage, inflammation, and impaired angiogenesis.