[HTML][HTML] Recombinant angiopoietin-1 restores higher-order architecture of growing blood vessels in mice in the absence of mural cells

A Uemura, M Ogawa, M Hirashima… - The Journal of …, 2002 - Am Soc Clin Investig
A Uemura, M Ogawa, M Hirashima, T Fujiwara, S Koyama, H Takagi, Y Honda, SJ Wiegand…
The Journal of clinical investigation, 2002Am Soc Clin Investig
Interactions between endothelial cells (ECs) and perivascular mural cells (MCs) via
signaling molecules or physical contacts are implicated both in vascular remodeling and
maintenance of vascular integrity. However, it remains unclear how MCs regulate the
morphogenic activity of ECs to form an organized vascular architecture, comprising distinct
artery, vein, and capillary, from a simple mesh-like network. A clear elucidation of this
question requires an experimental model system in which ECs are separated from MCs and …
Interactions between endothelial cells (ECs) and perivascular mural cells (MCs) via signaling molecules or physical contacts are implicated both in vascular remodeling and maintenance of vascular integrity. However, it remains unclear how MCs regulate the morphogenic activity of ECs to form an organized vascular architecture, comprising distinct artery, vein, and capillary, from a simple mesh-like network. A clear elucidation of this question requires an experimental model system in which ECs are separated from MCs and yet form vascular structures. Here we report that injection of an antagonistic mAb against PDGFR-β into murine neonates provides such an experimental system in the retina by completely blocking MC recruitment to developing vessels. While a vascular network was formed even in the absence of MCs, it was poorly remodeled and leaky. Using this vascular system ideal for direct assessment of the activities of MC-derived molecules, we show that addition of recombinant modified angiopoietin-1 restored a hierarchical vasculature, and also rescued retinal edema and hemorrhage in the complete absence of MCs. These observations demonstrate the potential of Ang1 as a new therapeutic modality for MC dropout in diseases such as diabetic retinopathies.
The Journal of Clinical Investigation