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Deletion of macrophage focal adhesion kinase signaling impairs neither arteriogenesis nor angiogenesis in the mouse ischemic hindlimb model
Author(s) -
Murrell Kelsey Paige,
Meisner Joshua,
Bouton Amy,
Price Richard
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.902.7
Subject(s) - arteriogenesis , angiogenesis , medicine , myeloid , perfusion , focal adhesion , neovascularization , myogenesis , cancer research , skeletal muscle , phosphorylation , biology , microbiology and biotechnology
We tested whether the myeloid specific deletion of focal adhesion kinase (FAK Δmyeloid ), which regulates macrophage differentiation and motility, impairs arteriogenesis and perfusion restoration. Laser doppler perfusion imaging showed a significant increase in perfusion recovery in FAK Δmyeloid 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 FAK Δmyeloid [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 FAK Δmyeloid vs 2.36 ± 0.32/2.06 ± 0.17 for WT control soleus, 1.57 ± 0.32/1.41 ± 0.18 for FAK Δmyeloid vs. 1.71 ± 0.32/1.46 ± 0.22 for WT oxidative gastrocnemius, and 0.98 ± 0.24/0.77 ± 0.13 for FAK Δmyeloid 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.