Coronary endothelial proliferation and morphogenesis are regulated by a VEGF-mediated pathway.
Though development of the coronary vasculature is a critical event during embryogenesis, the molecular mechanisms that regulate its formation are not well characterized. Two unique approaches were used to investigate interactions between cardiac myocytes and proepicardial (PE) cells, which are the coronary anlagen. One of these experimental approaches used a 3-D collagen scaffold system on which specific cell-cell and cell-matrix interactions were studied. The other approach used a whole heart culture system that allowed for the analysis of epicardial to mesenchymal transformation (EMT). The VEGF signaling system has been implicated previously as an important regulator of coronary development. Our results demonstrated that a specific isoform of VEGF-A, VEGF(164), increased PE-derived endothelial cell proliferation and also increased EMT. However, VEGF-stimulated endothelial cells did not robustly coalesce into endothelial tubes as they did when cocultured with cardiac myocytes. Interestingly, blocking VEGF signaling via flk-1 inhibition reduced endothelial tube formation despite the presence of cardiac myocytes. These results indicate that VEGF signaling is complex during coronary development and that combinatorial signaling by other VEGF-A isoforms or other flk-1-binding VEGFs are likely to regulate endothelial tube formation.
Nesbitt
Tresa L
TL
Departments of Cell and Developmental Biology and Surgery, University of South Carolina School of Medicine, Columbia, South Carolina, USA.
Roberts
Andrea
A
Tan
Hong
H
Junor
Lorain
L
Yost
Michael J
MJ
Potts
Jay D
JD
Dettman
Robert W
RW
Goodwin
Richard L
RL
D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D002645:Chickens; D003094:Collagen; D003331:Coronary Vessels / Q000166:cytology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D051379:Mice; D009024:Morphogenesis / Q000502:physiology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology*; D009924:Organ Culture Techniques; D010496:Pericardium / Q000166:cytology / Q000502:physiology; D020033:Protein Isoforms / Q000378:metabolism; D011784:Quail; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A; D003094:Collagen; D040301:Vascular Endothelial Growth Factor Receptor-2