Deletion of macrophage focal adhesion kinase signaling impairs neither arteriogenesis nor angiogenesis in the mouse ischemic hindlimb model

Abstract

We tested whether the myeloid specific deletion of focal adhesion kinase (FAKΔmyeloid), which regulates macrophage differentiation and motility, impairs arteriogenesis and perfusion restoration. Laser doppler perfusion imaging showed a significant increase in perfusion recovery in FAKΔmyeloid as compared to WT mice (n=6/5, p=0.011) after unilateral femoral artery ligation. Gracilis collateral arteries showed no differences in end‐state (day 28) or baseline (non‐ischemic limb) diameter between FAKΔmyeloid [88.4 ± 11.2 μm/42.1 ± 6.5 μm (ischemic/non‐ischemic)] and WT mice [92.4 ± 1.0 μm/40.4 ± 4.7 μm], and there were no differences in angiogenesis in the ischemic calf muscles (capillary:muscle fiber ratio of 2.42 ± 0.20/2.24 ± 0.25 ischemic/non‐ischemic for FAKΔmyeloid vs 2.36 ± 0.32/2.06 ± 0.17 for WT control soleus, 1.57 ± 0.32/1.41 ± 0.18 for FAKΔmyeloid vs. 1.71 ± 0.32/1.46 ± 0.22 for WT oxidative gastrocnemius, and 0.98 ± 0.24/0.77 ± 0.13 for FAKΔmyeloid vs. 0.75 ± 0.03/0.75 ± 0.07 for WT glycolytic gastrocnemius). In conclusion, FAK in myeloid cells does not regulate arteriogenesis or angiogenesis but may affect perfusion recovery through alternative means, such as improved muscle regeneration and/or decreased necrosis. Supported by NIH R21HL098632, AHA 10GRNT3490001, the UVA Cancer Center (CCSG P30 CA44579 and Patients and Friends Fund), and the Arnold and Mabel Beckman Foundation Scholars Program.