Chorionic gonadotropin stimulation of angiogenesis and pericyte recruitment.
BACKGROUND
During the periimplantation period, human chorionic gonadotropin (hCG) plays a key role by increasing the uterine blood flow through uterine vessel vasodilatation but also through angiogenesis. Indeed, we previously demonstrated that hCG contributes to endothelial cell recruitment and vessel formation.


OBJECTIVE
In this study, hCG was proposed as an arteriogenic factor that could promote perivascular cell recruitment and vessel stabilization.


METHODS
The aortic ring assay, a three-dimensional ex vivo angiogenesis system mimicking all the steps of the angiogenesis process was used to study the impact of hCG on pericyte recruitment and vessel maturation.


METHODS
The study was conducted at a university hospital laboratory.


METHODS
Perivascular cell proliferation, migration, and apposition were quantified by computerized image analysis.


RESULTS
Physiological concentrations of hCG (10-400 IU/ml) significantly enhanced pericyte sprouting and migration and gave rise to the maturation and coverage of endothelial capillaries. In a three-dimensional coculture model of endothelial and perivascular cells, hCG enhanced vessel tube formation and endothelial/mural cell adhesion. In addition, hCG stimulated the proliferation of human umbilical vein endothelial cells and smooth muscle cells. The specificity of these effects was determined by using an anti-hCG blocking antibody. Signaling pathways implicated on this hCG effect is protein kinase A and phospholipase C/protein kinase C dependent for the proliferative effect but only phospholipase C/protein kinase C for the migrative process.


CONCLUSIONS
Our findings highlight a novel paracrine role of this early embryonic signal in vessel maturation by stimulating perivascular cell recruitment, migration, and proliferation.
Berndt
Sarah
S
Department of Obstetrics and Gynecology, Centre Hospitalier Regional, Laboratory of Tumor and Development Biology, University of Liège, B-4000 Liège, Belgium.
Blacher
Silvia
S
Perrier d'Hauterive
Sophie
S
Thiry
Marc
M
Tsampalas
Marie
M
Cruz
André
A
Péqueux
Christel
C
Lorquet
Sophie
S
Munaut
Carine
C
Noël
Agnès
A
Foidart
Jean-Michel
JM
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D020286:Pericytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D014599:Uterus / Q000098:blood supply / Q000502:physiology
D006063:Chorionic Gonadotropin; D011994:Recombinant Proteins