Combined Endothelial and Skeletal Myofiber VEGF Gene Deletion Leads to Capillary Regression in Adult Mouse Hind Limb Muscle

Abstract

In adult mice, the importance of vascular endothelial growth factor (VEGF) for maintaining skeletal muscle capillaries is unclear. We hypothesized that deletion of the VEGF gene, targeted simultaneously to both endothelial cells and myofibers, would lead to a loss of capillaries in locomotor muscles.MethodsCapillary to fiber ratio (C:F), fiber‐cross sectional area (FCSA), and fiber‐type composition were measured in soleus, plantaris and gastrocnemius cryo‐sections from wild type (WT) and HSA‐Cre‐ERT2 X VEGFLoxP x PDGFb‐iCre‐ERT2 (EC+MyoVEGF−/−) mice. C:F was decreased in soleus from EC+MyoVEGF−/− mice compared to WT (WT, 1.64 ± 0.19, EC+MyoVEGF−/− 1.20 ± 0.19, n=3–9, p < 0.05). FCSA increased in both EC+MyoVEGF−/− soleus and plantaris (soleus: WT, 1953 ± 347 μm2, EC+MyoVEGF−/−, 3148 ± 543 μm2, plantaris: WT, 1731 ± 189 μm2, EC+MyoVEGF−/−, 3261 ± 803 μm2, n=3–9, p < 0.05). EC+MyoVEGF−/− mice also revealed a shift from type IIB to type IIA fibers in the plantaris (type IIB: WT, 66 ± 7 %, EC+MyoVEGF−/−, 48 ± 8 %, type IIA: WT, 19 ± 4%, EC+MyoVEGF−/−, 36 ± 16%, n=3–9, p < 0.05). Unlike previously reported studies in adult skeletal myofiber VEGF‐deficient mice, capillary regression does occur in adult skeletal muscle when VEGF expression is inhibited in both endothelial cells and myofibers.