Relationship between vascular development and vascular differentiation during liver organogenesis in humans.
OBJECTIVE
The complex vascular architecture characteristic of the normal adult liver is progressively acquired during the fetal life. In this study, we aimed to evaluate the relationship between angiogenesis and vascular differentiation during liver organogenesis.


METHODS
We studied, in 51 fetuses of different gestational ages, the expression of markers of endothelial cell differentiation, integrins, pro- and anti-angiogenic extracellular matrix components, vascular endothelial growth factor (VEGF) and its receptors.


RESULTS
Three main stages in the development of the vascular architecture of the liver were identified: (a) from 5 to 10 gestation weeks (GW), no evidence of de novo angiogenesis was detected; the vessels present in the liver primordium were the precursors of portal veins and sinusoids, deriving from preexisting vessels; (b) from 10 to 25 GW, angiogenesis and vasculogenesis resulted in the development of, respectively, arteries and intra-portal capillaries, while portal veins and hepatic sinusoids followed a differentiation process; (c) after 25 GW, little changes were detected in the various vascular compartments. The maximal expression of VEGF and its receptors was from 5 to 25 GW.


CONCLUSIONS
The development of the hepatic vascular architecture is a multistep process combining angiogenesis, vasculogenesis and vascular differentiation, regulated by specific growth and differentiation factors including VEGF.
Gouysse
Géraldine
G
Service Central d'Anatomie et Cytologie Pathologiques, Hôpital Edouard Herriot, 69437 Lyon Cedex 03, France.
Couvelard
Anne
A
Frachon
Sophie
S
Bouvier
Raymonde
R
Nejjari
Mimoun
M
Dauge
Marie Christine
MC
Feldmann
Gérard
G
Hénin
Dominique
D
Scoazec
Jean Yves
JY
D015415:Biomarkers; D001808:Blood Vessels / Q000196:embryology; D002454:Cell Differentiation / Q000502:physiology; D004622:Embryo, Mammalian / Q000166:cytology; D005314:Embryonic and Fetal Development; D016228:Endothelial Growth Factors / Q000378:metabolism; D004730:Endothelium, Vascular / Q000196:embryology; D006801:Humans; D016023:Integrins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008099:Liver / Q000196:embryology*; D008102:Liver Circulation; D008222:Lymphokines / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D042442:Vascular Endothelial Growth Factors
D015415:Biomarkers; D016228:Endothelial Growth Factors; D016023:Integrins; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2