Inhibition of delta-like-4-mediated signaling impairs reparative angiogenesis after ischemia.

ABSTRACT:

Rationale

Notch signaling regulates vascular development. However, the implication of the Notch ligand Delta-like 4 (Dll4) in postischemic angiogenesis remains unclear.

Objective

We investigated the role of Dll4/Notch signaling in reparative angiogenesis using a mouse model of ischemia.

Methods and results

We found Dll4 weakly expressed in microvascular endothelial cells of normoperfused muscles. Conversely, Dll4 is upregulated following ischemia and localized at the forefront of sprouting capillaries. We analyzed the effect of inhibiting endogenous Dll4 by intramuscular injection of an adenovirus encoding the soluble form of Dll4 extracellular domain (Ad-sDll4). Dll4 inhibition caused the formation of a disorganized, low-perfused capillary network in ischemic muscles

SUBMITTER: Al Haj Zen A 

PROVIDER: S-EPMC2917749 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature