Role of VEGF family members and receptors in coronary vessel formation.
The specific roles of vascular endothelial growth factor (VEGF) family members and their receptors (VEGFRs) in coronary vessel formation were studied. By using the quail heart explant model, we found that neutralizing antibodies to VEGF-B or VEGF-C inhibited tube formation on the collagen gel more than anti-VEGF-A. Soluble VEGFR-1, a receptor for VEGF-A and -B, inhibited tube formation by 87%, a finding consistent with that of VEGF-B inhibition. In contrast, addition of soluble VEGFR-2, a receptor for VEGF family members A, C, D, and E, inhibited tube formation by only 43%. Acidic FGF-induced tube formation dependency on VEGF was demonstrated by the attenuating effect of a soluble VEGFR-1 and -2 chimera. The localization of VEGF R-2 and R-3 was demonstrated by in situ hybridization of serial sections, which documented marked accumulations of transcripts for both receptors at the base of the truncus arteriosus coinciding with the temporal and spatial formation of the coronary arteries by means of ingrowth of capillary plexuses. This finding suggests that both VEGFR-2 and R-3 may play a role in the formation of the coronary artery roots. In summary, these experiments document a role for multiple members of the VEGF family and their receptors in formation of the coronary vascular bed.
Tomanek
Robert J
RJ
Department of Anatomy, University of Iowa, Iowa City, Iowa 52242, USA. robert-tomanek@uiowa.edu
Holifield
Jennifer S
JS
Reiter
Rebecca S
RS
Sandra
Alexander
A
Lin
Jim J-C
JJ
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002642:Chick Embryo; D003331:Coronary Vessels / Q000196:embryology* / Q000502:physiology; D003370:Coturnix; D016228:Endothelial Growth Factors / Q000235:genetics* / Q000276:immunology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000276:immunology; D008222:Lymphokines / Q000235:genetics* / Q000276:immunology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A; D042561:Vascular Endothelial Growth Factor B; D042582:Vascular Endothelial Growth Factor C; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics* / Q000276:immunology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000276:immunology; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000235:genetics / Q000276:immunology; D042442:Vascular Endothelial Growth Factors
D000906:Antibodies; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042561:Vascular Endothelial Growth Factor B; D042582:Vascular Endothelial Growth Factor C; D042442:Vascular Endothelial Growth Factors; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3