Dietary restriction promotes vessel maturation in a mouse astrocytoma

Mature vasculature contains an endothelial cell lining with a surrounding sheath of pericytes/vascular smooth muscle cells (vsmcs). tumor vessels are immature and lack a pericyte sheath. colocalization of vascular endothelial growth factor receptor 2 (vegfr-2) and platelet-derived growth factor receptor beta (pdgf-rβ) reduces pericyte ensheathment of tumor vessels. we found that a 30 dietary restriction (dr) enhanced vessel maturation in the mouse ct-2a astrocytoma. dr reduced microvessel density and vegf expression in the astrocytoma,while increasing recruitment of pericytes,positive for alpha-smooth muscle actin (α-sma). moreover,dr reduced colocalization of vegf-r2 and pdgf-r,but did not reduce total pdgf-rβ expression. these findings suggest that dr promoted vessel normalization by preventing vegf-induced inhibition of the pdgf signaling axis in pericytes. dr appears to shift the tumor vasculature from a leaky immature state to a more mature state. we suggest that vessel normalization could improve delivery of therapeutic drugs to brain tumors. copyright © 2012 ivan urits et al.