2,3,7,8-tetrachlorodibenzo-p-dioxin reduces myocardial hypoxia and vascular endothelial growth factor expression during chick embryo development

✍ Scribed by Irena D. Ivnitski-Steele; Andrea Sanchez; Mary K. Walker

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 401 KB
• Volume: 70
• Category: Article
• ISSN: 1542-0752
• DOI: 10.1002/bdra.10151

✦ Synopsis

Abstract

BACKGROUND

Previous research has demonstrated that 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) induces cardiomyocyte growth arrest, thinner ventricle walls, and reduced number and size of coronary arteries during chick embryogenesis. Coronary vascular development is believed to be mediated, in part, by myocardial oxygen gradients and a subsequent increase in hypoxia‐inducible factor 1α (HIF‐1α) and vascular endothelial growth factor‐A (VEGF‐A) expression. We investigated whether TCDD inhibition of coronary development was associated with altered myocardial oxygen status and reduced cardiac HIF‐1α and VEGF‐A.

METHODS

Chick embryos were exposed to 15% or 20% O~2~ for 24 hr from incubation days 9–10 or were injected with control (corn oil) or 0.24 pmol TCDD/gm egg on day 0. On day 9, embryos were injected with control (0.9% NaCl) or EF5, a tissue hypoxia marker, and cardiac binding of EF5 was determined by immunohistochemistry on day 10. In addition, embryo hearts were analyzed for VEGF‐A mRNA by in situ hybridization and quantitative RT‐PCR, and for HIF‐1α mRNA by quantitative RT‐PCR.

RESULTS

Cardiac binding of EF5 was significantly increased in embryos exposed to 15% O~2~, compared to embryos exposed to 20% O~2~. In contrast, TCDD‐exposed embryos exhibited significantly reduced binding of EF5 in the heart, compared to controls. Similarly, cardiac expression of HIF‐1α and VEGF‐A were increased following hypoxia and tended to be decreased following TCDD exposure.

CONCLUSIONS

These results suggest that the myocardium may be a target of TCDD toxicity, resulting in reduced myocardial hypoxia, and HIF‐1α and VEGF‐A expression believed necessary for normal coronary development. Birth Defects Research (Part A), 2004. © 2004 Wiley‐Liss, Inc.