RGD Reference Report - Aryl hydrocarbon receptor null mice develop cardiac hypertrophy and increased hypoxia-inducible factor-1alpha in the absence of cardiac hypoxia. - Rat Genome Database

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Aryl hydrocarbon receptor null mice develop cardiac hypertrophy and increased hypoxia-inducible factor-1alpha in the absence of cardiac hypoxia.

Authors: Thackaberry, E A  Gabaldon, D M  Walker, M K  Smith, S M 
Citation: Thackaberry EA, etal., Cardiovasc Toxicol. 2002;2(4):263-74. doi: 10.1385/ct:2:4:263.
RGD ID: 401784499
Pubmed: PMID:12665660   (View Abstract at PubMed)
DOI: DOI:10.1385/ct:2:4:263   (Journal Full-text)

The aryl hydrocarbon receptor (AhR) is a member of the basic helix loop helix PAS (Per-ARNT-SIM) transcription family, which also includes hypoxiainducible factor-1alpha (HIF-1alpha) and its common dimerization partner AhR nuclear translocator (ARNT). Following ligand activation or hypoxia, AhR or HIF-1alpha, respectively, translocate into the nucleus, dimerize with ARNT, and regulate gene expression. Mice lacking the AhR have been shown previously to develop cardiac enlargement. In cardiac hypertrophy, it has been suggested that the myocardium becomes hypoxic, increasing HIF-1alpha stabilization and inducing coronary neovascularization, however, this mechanism has not been demonstrated in vivo. The purpose of this study was to investigate the cardiac enlargement reported in AhR(-/-) mice and to determine if it was associated with myocardial hypoxia and subsequent activation of the HIF-1alpha pathway. We found that AhR(-/-) mice develop significant cardiac hypertrophy at 5 mo. However, this cardiac hypertrophy was not associated with myocardial hypoxia. Despite this finding, cardiac hypertrophy in AhR(-/-) mice was associated with increased cardiac HIF-1alpha protein expression and increased mRNA expression of the neovascularization factor vascular endothelial growth factor (VEGF). These data demonstrate that the development of cardiac hypertrophy in AhR(-/-) mice not associated with myocardial hypoxia, but is correlated with increased cardiac HIF-1alpha protein and VEGF mRNA expression.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
AHRHumanCardiomegaly  ISOAhr (Mus musculus) RGD 
AhrRatCardiomegaly  ISOAhr (Mus musculus) RGD 
AhrMouseCardiomegaly  IMP  RGD 
HIF1AHumanCardiomegaly  ISOHif1a (Mus musculus) RGD 
Hif1aRatCardiomegaly  ISOHif1a (Mus musculus) RGD 
Hif1aMouseCardiomegaly  IGIRGDID:2074 RGD 
VEGFAHumanCardiomegaly  ISOVegfa (Mus musculus) RGD 
VegfaRatCardiomegaly  ISOVegfa (Mus musculus) RGD 
VegfaMouseCardiomegaly  IGIRGDID:2074 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ahr  (aryl hydrocarbon receptor)
Hif1a  (hypoxia inducible factor 1 subunit alpha)
Vegfa  (vascular endothelial growth factor A)

Genes (Mus musculus)
Ahr  (aryl-hydrocarbon receptor)
Hif1a  (hypoxia inducible factor 1, alpha subunit)
Vegfa  (vascular endothelial growth factor A)

Genes (Homo sapiens)
AHR  (aryl hydrocarbon receptor)
HIF1A  (hypoxia inducible factor 1 subunit alpha)
VEGFA  (vascular endothelial growth factor A)


Additional Information