Previous work in our laboratory has shown that angiogenesis in skeletal muscle induced by mechanical stimuli can occur via two morphologically distinct pathways (Egginton et al. 2001), and that in the rat both these pathways are associated with increased levels of VEGF (Rivilis et al. 2002).Recent work suggests that the mouse responds similarly (unpublished data).

To investigate the importance of this increase in VEGF, we pharmacologically blocked circulating VEGF using the novel compound VEGF-trap (Regeneron Inc.), which consists of VEGF receptor portions fused to human immunoglobulin Fc.The m. extensor digitorum longus (EDL) of mice was subjected to two forms of mechanical stimulus 1) increased shear stress caused by oral administration of prazosin 2) muscle overload from surgical extirpation of the synergistic m. tibialis anterior (under hypnorm/hypnoval anaesthesia I.P.). Animals were humanely killed 14 days after the start of treatment.

Without co-administration of VEGF-trap, the capillary to fibre ratio (C:F) increased by 26 % (P = 0.029, Student’s t test, n = 3) after prazosin treatment, and by 28 % (P = 0.008, n = 3) after extirpation compared to controls.Subcutaneous administration of VEGF-trap completely abolished the increases in C:F seen in both models, with all groups of animals showing no significant difference in C:F from untreated controls (n = 3 in all groups).

These data demonstrate that VEGF is essential for angiogenesis in vivo in response to two different mechanical stimuli.

This work was funded by the British Heart Foundation