Role of VEGF family members and receptors in coronary vessel formation

• Published in: Developmental dynamics Vol. 225; no. 3; pp. 233 - 240
• Main Authors: Tomanek, Robert J., Holifield, Jennifer S., Reiter, Rebecca S., Sandra, Alexander, Lin, Jim J.‐C.
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 01-11-2002
• Subjects: angiogenesis; Animals; Antibodies - pharmacology; Chick Embryo; Coronary Vessels - embryology; Coronary Vessels - physiology; Coturnix; Endothelial Growth Factors - genetics; Endothelial Growth Factors - immunology; flk‐1; flt‐1; flt‐4; Gene Expression Regulation, Developmental - physiology; in situ hybridization; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - immunology; Lymphokines - genetics; Lymphokines - immunology; Neovascularization, Physiologic - physiology; quail; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor B; Vascular Endothelial Growth Factor C; Vascular Endothelial Growth Factor Receptor-1 - genetics; Vascular Endothelial Growth Factor Receptor-1 - immunology; Vascular Endothelial Growth Factor Receptor-2 - genetics; Vascular Endothelial Growth Factor Receptor-2 - immunology; Vascular Endothelial Growth Factor Receptor-3 - genetics; Vascular Endothelial Growth Factor Receptor-3 - immunology; Vascular Endothelial Growth Factors; vasculogenesis; VEGF‐A; VEGF‐B; VEGF‐C
• ISSN: 1058-8388; 1097-0177
• DOI: 10.1002/dvdy.10158

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. © 2002 Wiley‐Liss, Inc.