TY - JOUR
T1 - Pericytes regulate VEGF-induced endothelial sprouting through VEGFR1
AU - Eilken, Hanna M.
AU - Diéguez-Hurtado, Rodrigo
AU - Schmidt, Inga
AU - Nakayama, Masanori
AU - Jeong, Hyun Woo
AU - Arf, Hendrik
AU - Adams, Susanne
AU - Ferrara, Napoleone
AU - Adams, Ralf H.
N1 - Funding Information:
Funding was provided by the Max Planck Society, the University of Münster and the Deutsche Forschungsgemeinschaft (FOR 2325, SFB 1009, and Cells-in-Motion Cluster of Excellence; EXC-CiM). H.M.E. was partially funded by the DFG priority program SPP 1190 (The tumor-vessel interface) and R.D.-H. by the European Union (Marie Curie ITN VESSEL). We are grateful to Dr. Martin Stehling for expert advice in flow cytometry experiments and to Dr. Ann Seynhaeve for the contribution to the initial characterization of Pdgfrb-CreERT2 founder animals.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Pericytes adhere to the abluminal surface of endothelial tubules and are required for the formation of stable vascular networks. Defective endothelial cell-pericyte interactions are frequently observed in diseases characterized by compromised vascular integrity such as diabetic retinopathy. Many functional properties of pericytes and their exact role in the regulation of angiogenic blood vessel growth remain elusive. Here we show that pericytes promote endothelial sprouting in the postnatal retinal vasculature. Using genetic and pharmacological approaches, we show that the expression of vascular endothelial growth factor receptor 1 (VEGFR1) by pericytes spatially restricts VEGF signalling. Angiogenic defects caused by pericyte depletion are phenocopied by intraocular injection of VEGF-A or pericyte-specific inactivation of the murine gene encoding VEGFR1. Our findings establish that pericytes promote endothelial sprouting, which results in the loss of side branches and the enlargement of vessels when pericyte function is impaired or lost.
AB - Pericytes adhere to the abluminal surface of endothelial tubules and are required for the formation of stable vascular networks. Defective endothelial cell-pericyte interactions are frequently observed in diseases characterized by compromised vascular integrity such as diabetic retinopathy. Many functional properties of pericytes and their exact role in the regulation of angiogenic blood vessel growth remain elusive. Here we show that pericytes promote endothelial sprouting in the postnatal retinal vasculature. Using genetic and pharmacological approaches, we show that the expression of vascular endothelial growth factor receptor 1 (VEGFR1) by pericytes spatially restricts VEGF signalling. Angiogenic defects caused by pericyte depletion are phenocopied by intraocular injection of VEGF-A or pericyte-specific inactivation of the murine gene encoding VEGFR1. Our findings establish that pericytes promote endothelial sprouting, which results in the loss of side branches and the enlargement of vessels when pericyte function is impaired or lost.
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U2 - 10.1038/s41467-017-01738-3
DO - 10.1038/s41467-017-01738-3
M3 - Article
C2 - 29146905
AN - SCOPUS:85034418523
SN - 2041-1723
VL - 8
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1574
ER -
