VEGF modulates early heart valve formation.
Although hypoxic and/or nutritional insults during gestation are believed to contribute to congenital heart defects, the mechanisms responsible for these anomalies are not understood. Given the role vascular endothelial growth factor (VEGF) plays in response to hypoxia, it is a likely candidate for mediating deleterious effects of embryonic hypoxia. The ectopic or overproduction of endogenous factors such as VEGF may contribute to specific heart defects. Here we compared hypoxia-induced precocious production of VEGF during early heart valve development to normal VEGF production. Mouse prevalvular cardiac endocardial cushions were explanted onto hydrated type I collagen gels under normoxic or hypoxic conditions. The extent of transformation of cardiac endothelium into mesenchyme was inversely correlated with the levels of VEGF during the various culture conditions. A soluble VEGF antagonist confirmed that endogenous production of VEGF was specific for blocking normal cushion mesenchyme formation. We further demonstrated that E10.5 endocardium retains the ability to transform into cardiac mesenchyme in the absence of endogenous VEGF.
Dor
Yuval
Y
Department of Molecular Biology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Klewer
Scott E
SE
McDonald
John A
JA
Keshet
Eli
E
Camenisch
Todd D
TD
D000818:Animals; D002478:Cells, Cultured; D003470:Culture Media; D004699:Endocardium / Q000166:cytology / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D006351:Heart Valves / Q000166:cytology / Q000187:drug effects / Q000196:embryology*; D000860:Hypoxia / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008954:Models, Biological; D009024:Morphogenesis; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology
D003470:Culture Media; D042461:Vascular Endothelial Growth Factor A