For patients with advanced vascular disease, improving the efficacy of arteriogenesis may provide an alternative to invasive bypass surgery. Ren et al. discovered that shifting the balance between extracellular signal-regulated kinase (ERK)1/2 and phosphoinositide 3-kinase (PI3K)-Akt1, two crucial signaling arms that are activated by VEGF, stimulates arterial growth in mouse and zebrafish models of vascular disease. ERK1/2 is highly activated in growing arteries. This is in contrast to the PI3K-Akt1 pathway, which is thought to have an arterial stabilizing effect. In mice and zebrafish with decreased VEGF responsiveness and ERK1/2 activity, researchers restored ERK1/2 activation by downregulating PI3K-Akt1 activity or by introducing a constitutively activating ERK1/2. Both approaches stimulate arterial development. Inhibiting the PI3K-Akt1 pathway in an atherosclerotic mouse model effectively stimulated arterial formation. Thus, the PI3K-Akt1 pathway is a potential drug target for vascular disease.
Ren
B
, Deng
Y
, Mukhopadhyay
A
, Lanahan
AA
, Zhuang
ZW
, Moodie
KL
, Mulligan-Kehoe
MJ
, Byzova
TV
, Peterson
RT
, Simons
M
(2010
). ERK1/2-Akt1 crosstalk regulates arteriogenesis in mice and zebrafish
. J. Clin. Invest
. Mar
8
[Epub ahead of print] [doi:10.1172/JCI39837].
