Adverse Outcome Pathway on Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF:
Interference with endogenous developmental processes that are regulated by the aryl hydrocarbon receptor (AHR), through sustained exogenous activation, causes molecular, structural, and functional cardiac abnormalities in avian, mammalian and piscine embryos; this cardiotoxicity ultimately leads to...
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| Format: | Elektronisch E-Book |
| Sprache: | English |
| Veröffentlicht: |
Paris
OECD Publishing
2019
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| Schriftenreihe: | OECD Series on Adverse Outcome Pathways
no.16 |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Zusammenfassung: | Interference with endogenous developmental processes that are regulated by the aryl hydrocarbon receptor (AHR), through sustained exogenous activation, causes molecular, structural, and functional cardiac abnormalities in avian, mammalian and piscine embryos; this cardiotoxicity ultimately leads to severe oedema and embryo death in birds and fish and some strains of rat. There have been numerous proposed mechanisms of action for this toxicity profile, many of which include the dysregulation of vascular endothelial growth factor (VEGF). This AOP describes the indirect suppression of VEGF expression through the sequestration of the aryl hydrocarbon receptor nuclear translocator (ARNT) by AHR. ARNT is common dimerization partner for both AHR and hypoxia inducible factor alpha (HIF-1α), which stimulates angiogenesis through the transcriptional regulation of VEGF. The suppression of VEGF thereby reduces cardiomyocyte and endothelial cell proliferation, altering cardiovascular morphology and reducing cardiac output, which ultimately leads to congestive heart failure and death. |
| Beschreibung: | 1 Online-Ressource (104 p.) |
| DOI: | 10.1787/063e1bf4-en |
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| spelling | Farhat, Amani VerfasserIn aut Adverse Outcome Pathway on Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF Amani, Farhat and Sean W., Kennedy Paris OECD Publishing 2019 1 Online-Ressource (104 p.) Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier OECD Series on Adverse Outcome Pathways no.16 Interference with endogenous developmental processes that are regulated by the aryl hydrocarbon receptor (AHR), through sustained exogenous activation, causes molecular, structural, and functional cardiac abnormalities in avian, mammalian and piscine embryos; this cardiotoxicity ultimately leads to severe oedema and embryo death in birds and fish and some strains of rat. There have been numerous proposed mechanisms of action for this toxicity profile, many of which include the dysregulation of vascular endothelial growth factor (VEGF). This AOP describes the indirect suppression of VEGF expression through the sequestration of the aryl hydrocarbon receptor nuclear translocator (ARNT) by AHR. ARNT is common dimerization partner for both AHR and hypoxia inducible factor alpha (HIF-1α), which stimulates angiogenesis through the transcriptional regulation of VEGF. The suppression of VEGF thereby reduces cardiomyocyte and endothelial cell proliferation, altering cardiovascular morphology and reducing cardiac output, which ultimately leads to congestive heart failure and death. Environment Social Issues/Migration/Health Kennedy, Sean W... MitwirkendeR ctb FWS01 ZDB-13-SOC FWS_PDA_SOC https://doi.org/10.1787/063e1bf4-en Volltext |
| spellingShingle | Farhat, Amani Adverse Outcome Pathway on Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF Environment Social Issues/Migration/Health |
| title | Adverse Outcome Pathway on Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF |
| title_auth | Adverse Outcome Pathway on Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF |
| title_exact_search | Adverse Outcome Pathway on Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF |
| title_full | Adverse Outcome Pathway on Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF Amani, Farhat and Sean W., Kennedy |
| title_fullStr | Adverse Outcome Pathway on Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF Amani, Farhat and Sean W., Kennedy |
| title_full_unstemmed | Adverse Outcome Pathway on Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF Amani, Farhat and Sean W., Kennedy |
| title_short | Adverse Outcome Pathway on Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF |
| title_sort | adverse outcome pathway on aryl hydrocarbon receptor activation leading to early life stage mortality via reduced vegf |
| topic | Environment Social Issues/Migration/Health |
| topic_facet | Environment Social Issues/Migration/Health |
| url | https://doi.org/10.1787/063e1bf4-en |
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