New pathways toward growing new arteries

Stimulating arteriogenesis, the growth of new arteries, in adults with cardiovascular disease is a holy grail of cardiology. Many efforts have focused on vascular endothelial growth factor (VEGF), which creates new blood vessels during embryonic development. However, VEGF has shown little success in adults, especially in those with cardiovascular disease or diabetes.

A team led by Michael Simons, M.D., the Robert W. Berliner Professor of Medicine and Cell Biology, and chief of Yale’s Section of Cardiovascular Medicine, focused instead on two interacting signaling pathways, ERK1/2 and PI3K. ERK1/2 is activated in growing arteries and suppressed in quiescent vessels, so the group searched for some PI3K inhibitory factor. In the April issue of The Journal of Clinical Investigation, they name the culprit, a PI3K-regulated enzyme known as Akt1. Suppressing Akt1 released the PI3K brake on ERK1/2 and successfully activated growth of new arteries in mice and zebrafish.

“Because we’ve located this inhibitory pathway, this opens the possibility of developing a new class of medication to grow new arteries,” Simons says. “The next step is to test this finding in a human clinical trial.”