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Multiple growth factors regulate coronary embryonic vasculogenesis
Author(s) -
Tomanek Robert J.,
Zheng Wei,
Peters Kevin G.,
Lin Pengnian,
Holifield Jennifer S.,
Suvarna Padma R.
Publication year - 2001
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.1137
Subject(s) - vasculogenesis , biology , quail , vascular endothelial growth factor , angiogenesis , microbiology and biotechnology , basic fibroblast growth factor , neutralizing antibody , receptor tyrosine kinase , growth factor , receptor , medicine , endocrinology , immunology , antibody , biochemistry , in vitro , signal transduction , endothelial stem cell , cancer research , vegf receptors
Mechanisms regulating coronary vascularization are not well understood. To test hypotheses regarding the influence of key growth factors and their interactions, we studied vascular tube formation (vasculogenesis) in collagen gels onto which quail embryonic ventricles were placed and incubated in the presence of growth factors or inhibitors. Vasculogenesis in this model is dependent on tyrosine kinase receptors, since tube formation was totally blocked by genestein. Tube formation was attenuated when anti‐bFGF or anti‐VEGF neutralizing antibodies were added to the medium and nearly completely inhibited when the both were added. The attenuation associated with anti‐VEGF was due primarily to a decrease in assembly of endothelial cells, while that associated with bFGF was primarily due to a reduction in endothelial cells. Soluble tie‐2, the receptor for angiopoietins, also had an inhibitory effect and, when added with either anti‐bFGF or anti‐VEGF, markedly attenuated tube formation. At optimal doses, tube formation was enhanced 6.5‐fold by bFGF and 2.5‐fold by VEGF over the controls. Each of these growth factors was dependent upon the other for optimal induction of tube formation, since neutralizing antibodies to one markedly reduced the potency of the other. VEGF potency was also markedly reduced when soluble tie‐2 was added to the medium. Tube formation was virtually totally blocked by exogenous TGF‐β at doses > 1 ng/ml, while neutralizing TGF‐β antibodies enhanced tube formation 2‐fold in the 30 ng–30 μg range. These data provide the first documentation of multiple growth factor regulation of coronary tube formation. © 2001 Wiley‐Liss, Inc.