Abstract
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 C57BL/6J and SV-129 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 C57BL/6J and SV-129 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, C57BL/6J 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 SV-129 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 SV-129 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 C57BL/6J mice compared to SV-129 mice, with the latter showing aggravated tissue damage, inflammation, and impaired angiogenesis.
Highlights
The terminal vessels of the vertebrate circulatory system are made up of arterioles, venules, and the capillary bed, with the latter being mandatory for maintaining the homeostasis of a living individual [1]
To compare the angiogenic potential of the two different mouse strains, we followed a well-established model of hindlimb ischemia: the right femoral artery of C57BL/6J and SV-129 mice was occluded (FAL), leading to collateral growth in the upper leg and angiogenesis in the lower leg on the occluded side, while the left leg underwent a sham operation [25]
We found a significantly reduced number of neutrophils (MPO+ /DAPI+ ), neutrophil extracellular traps (NETs) (MPO+ /citrullinated histone H3 (CitH3)+ /DAPI+ ), and neutrophils, which are in the process of NET formation, in mice of the C57BL/6J strain in comparison to the SV-129 line in ischemic tissue (Figure 4)
Summary
The terminal vessels of the vertebrate circulatory system are made up of arterioles, venules, and the capillary bed, with the latter being mandatory for maintaining the homeostasis of a living individual [1]. The regulation of capillary bed growth in the adult individual plays a vital role in physiological conditions as well as in many acute and chronic diseases, such as wound healing, cancer, and inflammation [2,3,4]. In cancer, uncontrolled capillary growth facilitates the nutrition and survival of tumor cells and their blood-dependent metastatic spread, in wound healing, impaired angiogenesis causes chronic stagnancy of the healing process. Both promoting and inhibiting angiogenic processes are the object of different therapeutic approaches, dependent on the present pathology
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