Lactadherin promotes VEGF-dependent neovascularization
Résumé
Vascular endothelial growth factor (VEGF)-induced blood vessel growth is involved in both physiological and pathological angiogenesis and requires integrin-mediated signaling. We now show that an integrin-binding protein initially described in milk-fat globule, MFG-E8 (also known as lactadherin), is expressed in and around blood vessels and has a crucial role in VEGF-dependent neovascularization in the adult mouse. Using neutralizing antibodies and lactadherin-deficient animals, we show that lactadherin interacts with αvβ3 and αbβ5 integrins and alters both VEGF-dependent Akt phosphorylation and neovascularization. In the absence of VEGF, lactadherin administration induced αbβ3- and αvβ5-dependent Akt phosphorylation in endothelial cells in vitro and strongly improved postischemic neovascularization in vivo. These results show a crucial role for lactadherin in VEGF-dependent neovascularization and identify lactadherin as an important target for the modulation of neovascularization.
Mots clés
alphaVbeta5 integrin
binding protein
integrin
integrin binding protein
lactadherin
neutralizing antibody
protein kinase B
unclassified drug
vasculotropin
vitronectin receptor
angiogenesis
animal cell
animal experiment
animal model
animal tissue
article
controlled study
endothelium cell
female
leg ischemia
male
mouse
nonhuman
pathophysiology
priority journal
protein binding
protein expression
protein phosphorylation
protein protein interaction
signal transduction
vascularization
Analysis of Variance
Angiogenesis Inducing Agents
Animals
Antigens
Surface
Blotting
Southern
Crosses
Genetic
Female
Genetic Vectors
Humans
Integrin alphaVbeta3
Ischemia
Mice
Inbred C57BL
Milk Proteins
Muscle
Skeletal
Neovascularization
Physiologic
Phosphorylation
Protein-Serine-Threonine Kinases
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-akt
Signal Transduction
Vascular Endothelial Growth Factor A
Animalia