| 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) inhibition of coronary vasculogenesis is mediated, in part, by reduced responsiveness to endogenous angiogenic stimuli, including vascular endothelial growth factor A (VEGF-A). | |
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MedLine Citation:
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PMID: 15880788 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) exposure prior to chick embryo incubation (GD 0) induces dilated cardiomyopathy, and reduces myocardial hypoxia, vascular endothelial growth factor A (VEGF-A) expression, and coronary vascularization. We investigated whether reduced coronary vascularization 1) occurs in the absence of changes in cardiac morphology and 2) is associated with altered secretion of VEGF-A and/or an antivasculogenic factor. METHODS: Chicken eggs were treated with control (corn oil) or TCDD (0.075-0.3 pmol of TCDD/gm) on GD 5. In vivo cardiac morphology and artery number were determined on GD 10, while in vitro vascular outgrowth and VEGF-A secretion were determined from cardiac explants on GD 6. Effects of recombinant VEGF-A (rcVEGF-A), soluble flt-1 (sFlt-1) receptor plus rcVEGF-A, and control conditioned media were assessed in TCDD explants, while effects of TCDD-conditioned media was assessed in control explants. RESULTS: TCDD reduced coronary artery number in vivo by 53 +/- 8% and induced a dose-related reduction in tube outgrowth in vitro, but had no effect on cardiac morphology. All TCDD doses reduced explant VEGF-A secretion equally (43 +/- 3%), compared to control. sFlt-1 blocked outgrowth in control cultures and blocked rcVEGF-A-mediated rescue of outgrowth in TCDD explants. Control conditioned media partially rescued outgrowth from TCDD explants, while conditioned media from TCDD explants had no effect on controls. CONCLUSIONS: TCDD inhibition of coronary vascularization can occur in the absence of changes in cardiac morphology and is associated with reduced VEGF-A secretion but not an antivasculogenic factor. Since control media only partly rescues TCDD's inhibitory effect, we suggest that TCDD-exposed endothelial cells are less responsive to vasculogenic stimuli. |
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Authors:
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Irena D Ivnitski-Steele; Megan Friggens; Miquella Chavez; Mary K Walker |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Birth defects research. Part A, Clinical and molecular teratology Volume: 73 ISSN: 1542-0752 ISO Abbreviation: Birth Defects Res. Part A Clin. Mol. Teratol. Publication Date: 2005 Jun |
Date Detail:
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Created Date: 2005-06-13 Completed Date: 2005-10-04 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 101155107 Medline TA: Birth Defects Res A Clin Mol Teratol Country: United States |
Other Details:
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Languages: eng Pagination: 440-6 Citation Subset: IM |
Copyright Information:
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(c) 2005 Wiley-Liss, Inc. |
Affiliation:
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College of Pharmacy, University of New Mexico, Albuquerque, NM 87131, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Angiogenesis Inducing Agents
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pharmacology* Animals Chick Embryo Coronary Vessels / drug effects*, embryology Fibroblast Growth Factor 2 / pharmacology Tetrachlorodibenzodioxin / toxicity* Vascular Endothelial Growth Factor A / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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P30 ES 012072/ES/NIEHS NIH HHS; R01 ES 09804/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Angiogenesis Inducing Agents; 0/Vascular Endothelial Growth Factor A; 103107-01-3/Fibroblast Growth Factor 2; 1746-01-6/Tetrachlorodibenzodioxin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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