Mast cells increase in number following muscle overload but their activation is not critical to the angiogenic process

In skeletal muscle, mast cells reside in close proximity to capillaries and release factors capable of initiating angiogenesis. Overload (OL) of skeletal muscle induces angiogenesis as evidenced by increased capillary to muscle fibre ratio (C:F). We determined if mast cells play a role in the angiogenic response to muscle OL. OL of the extensor digitorum longus (EDL) was induced in male rats through extirpation of the tibialis anterior muscle. EDL was removed after 1, 2, 4 and 7 days of OL and stained with toluidine blue to visualize mast cells. Mast cell number in OL muscle did not differ from that seen in sham animals at the 1, 2 and 4 day timepoints but was significantly increased following 7 days OL. To determine if mast cells are critical to the angiogenic response, animals received Cromolyn (Cr) (160mg/kg), an inhibitor of mast cell degranulation, by i.p. injection pre‐surgery and again one day post surgery. 14 days OL and 14 days OL + Cr significantly increased C:F compared to sham + vehicle (2.64±0.13 and 2.48±0.10 vs. 1.69±0.06). Matrix metalloproteinase‐2 protein was assessed as it is crucial to OL‐induced angiogenesis. Levels were elevated after 7 days OL and 7 days OL + Cr compared to sham + vehicle (1.64±0.20 and 1.49±0.17 vs. 1.11±0.16). Our results indicate that EDL mast cell number increases after 7 days OL. However, mast cell activation is not critical to the angiogenic response. Funding by NSERC and OGS. Grant Funding Source NSERC