In the new study, Shima's group examined mice engineered to make only single VEGF isoforms. These mice reveal that VEGF isoforms have opposing effects on growing vessel networks. Although all forms stimulated cell growth in vivo, mice that expressed only soluble VEGF had expanded microvessels with fewer branches. In contrast, microvessels in mice with only ECM-binding VEGF were narrow and branched excessively.
“Our results indicate that growth is integrated with tissues, because the tissue provides localized cues by depositing VEGF in precise spatial patterns,” says Ruhrberg. The road map is provided by ECM-bound VEGF, which attracted filopodia extending from the tip of a new vessel branch. Soluble VEGF did not remain where it was secreted, but rather traveled further away, thus stimulating expansion of existing vessels from a distance. The authors hope to raise awareness of isoform-specific effects for those considering the use of VEGF for therapy to increase or block angiogenesis. ▪