VEGF modulates early heart valve formation

Yuval Dor, Scott E. Klewer, John A. McDonald, Eli Keshet, Todd D. Camenisch

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)202-208
Number of pages7
JournalAnatomical Record - Part A Discoveries in Molecular, Cellular, and Evolutionary Biology
Volume271
Issue number1
DOIs
StatePublished - Mar 1 2003

Keywords

  • Development
  • Endocardial cushions
  • Heart
  • Hypoxia
  • VEGF

ASJC Scopus subject areas

  • Anatomy
  • Agricultural and Biological Sciences (miscellaneous)

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