title: VEGF modulates early heart valve formation.
abstract: 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.
authors.affiliation: Department of Molecular Biology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Dor
authors.forename: Scott E
authors.initials: SE
authors.lastname: Klewer
authors.forename: John A
authors.initials: JA
authors.lastname: McDonald
authors.forename: Eli
authors.initials: E
authors.lastname: Keshet
authors.forename: Todd D
authors.initials: TD
authors.lastname: Camenisch
mesh_terms: 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
chemical_list: D003470:Culture Media; D042461:Vascular Endothelial Growth Factor A