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Stimulation of coronary vasculogenesis/angiogenesis by hypoxia in cultured embryonic hearts
Author(s) -
Yue Xinping,
Tomanek Robert J.
Publication year - 1999
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/(sici)1097-0177(199909)216:1<28::aid-dvdy5>3.0.co;2-u
Subject(s) - vasculogenesis , angiogenesis , biology , vascular endothelial growth factor , hypoxia (environmental) , hyperoxia , vascular endothelial growth factor a , quail , endocrinology , medicine , microbiology and biotechnology , immunology , andrology , progenitor cell , cancer research , stem cell , chemistry , vegf receptors , organic chemistry , lung , oxygen
Abstract Hypoxia is known to stimulate vascular growth by up‐regulating vascular endothelial growth factor (VEGF), but little is known about the function of hypoxia in the development of the coronary vasculature, and the relationship between hypoxia and VEGF in this event. To test the effects of hypoxia and VEGF on coronary vasculogenesis/angiogenesis in the developing heart, ventricles from 6‐day‐old quail embryos were cultured on three‐dimensional collagen gels. After 2 days of growth in normal medium and 1 day of starvation in low serum medium (0.5% fetal bovine serum), the heart explants were further cultured under various oxygen levels for another 24, 48, and 72 hr. Angioblasts and endothelial cells, which migrated out from the heart explants, were identified by QH1 antibody using immunofluorescence and confocal microscopy. In the normoxic culture environment, the endothelial cells began to proliferate and migrate out from the heart explants after 3 days of growth; they formed tubes mainly after another 72 hr. In contrast, this vascular growth was accelerated under hypoxic conditions, as evidenced by increased tube formation with significant differences observed at 48 hr. On the other hand, hyperoxia delayed this process. Reverse transcription‐polymerase chain reaction results indicated that VEGF (including VEGF 122 , VEGF 166 , and VEGF 190 ) was up‐regulated in the heart explants under hypoxia and down‐regulated under hyperoxia. VEGF neutralizing antibody added to the culture medium partially blocked this vascular growth. We conclude from this study that hypoxia can stimulate or up‐regulate coronary vasculogenesis/angiogenesis and that VEGF signaling plays a major role in this event. Dev Dyn 1999;216:28–36. © 1999 Wiley‐Liss, Inc.