Vascular development is disrupted by endothelial cell-specific expression of the anti-apoptotic protein Bcl-2.
Endothelial cell (EC) apoptosis has been detected in remodelling blood vessels in vivo, and inhibition of EC apoptosis appears to alter vascular morphogenesis in vitro, suggesting that EC apoptosis may play a role in blood vessel remodelling. However, apoptotic EC are difficult to quantify in vivo, and studies of the incidence of EC apoptosis and the sites at which it occurs in vivo have produced contradictory results. Therefore, the specific biological roles played by EC apoptosis remain unclear. Here, we have used a transgenic approach to determine the biological function of EC apoptosis in vivo. Anti-apoptotic Bcl-2 transgenes were expressed in mice under control of the EC-specific tie2 promoter. These transgenic mice died during the second half of gestation. While the development and remodelling of large vessels including aortic arch arteries and great veins proceeded normally, abnormally dense and disorganised networks of small vessels were present in the skin and internal organs. In addition, vessel organisation and lumen formation were disrupted in the placental labyrinth. This study provides direct experimental evidence that endothelial cell apoptosis plays an essential role during embryogenesis. Our results suggest that EC apoptosis plays an important role in determining the structure of the microcirculation but may be dispensable for large vessel development.
Duval
Hélène
H
Department of Pathology, Cambridge University, Tennis Court Road, Cambridge CB2 1QP, UK.
Johnson
Nicola
N
Li
Jia
J
Evans
Amanda
A
Chen
Shuo
S
Licence
Diana
D
Skepper
Jeremy
J
Charnock-Jones
D Stephen
DS
Smith
Stephen
S
Print
Cristin
C
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D020169:Caspases / Q000096:biosynthesis / Q000235:genetics; D002417:Cattle; D042783:Endothelial Cells / Q000378:metabolism / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000002:abnormalities / Q000196:embryology*; D005260:Female; D005455:Fluorescent Antibody Technique; D005865:Gestational Age; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008833:Microcirculation / Q000002:abnormalities* / Q000648:ultrastructure; D018919:Neovascularization, Physiologic / Q000235:genetics*; D010920:Placenta / Q000002:abnormalities; D011247:Pregnancy; D049188:Prenatal Injuries / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D019076:Transgenes
D019253:Proto-Oncogene Proteins c-bcl-2; D020169:Caspases