Abstract | OBJECTIVE: METHODS AND RESULTS:
Ischemia was induced by femoral artery occlusion in wild-type and AHR-null mice. Ischemia-induced angiogenesis was markedly enhanced in AHR-null mice compared with that in wild-type animals. Ischemia-induced upregulation of the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and ARNT as well as that of target genes for these transcription factors, such as that for vascular endothelial growth factor ( VEGF), were also enhanced in AHR-null mice. Furthermore, the DNA binding activity of the HIF-1alpha-ARNT complex as well as the association of HIF-1alpha and ARNT with the VEGF gene promoter were increased by ischemia to a greater extent in AHR-null mice than in wild-type animals. CONCLUSIONS: Ablation of AHR resulted in enhancement of ischemia-induced angiogenesis. This effect was likely attributable in part to the associated enhancement of ischemia-induced VEGF expression, which in turn may be caused by an increased abundance and activity of the HIF-1alpha-ARNT heterodimer.
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Authors | Sahoko Ichihara, Yoshiji Yamada, Gaku Ichihara, Tamie Nakajima, Ping Li, Takahisa Kondo, Frank J Gonzalez, Toyoaki Murohara |
Journal | Arteriosclerosis, thrombosis, and vascular biology
(Arterioscler Thromb Vasc Biol)
Vol. 27
Issue 6
Pg. 1297-304
(Jun 2007)
ISSN: 1524-4636 [Electronic] United States |
PMID | 17413038
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Ahr protein, mouse
- Angiogenic Proteins
- Basic Helix-Loop-Helix Transcription Factors
- Carcinogens
- Hif1a protein, mouse
- Hypoxia-Inducible Factor 1, alpha Subunit
- RNA, Messenger
- Receptors, Aryl Hydrocarbon
- Vascular Endothelial Growth Factor A
- vascular endothelial growth factor A, mouse
- Aryl Hydrocarbon Receptor Nuclear Translocator
- Benzo(a)pyrene
- DNA
- Receptor, Platelet-Derived Growth Factor beta
- Receptors, Vascular Endothelial Growth Factor
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Topics |
- Angiogenic Proteins
(genetics, metabolism)
- Animals
- Aryl Hydrocarbon Receptor Nuclear Translocator
(genetics, metabolism)
- Basic Helix-Loop-Helix Transcription Factors
- Benzo(a)pyrene
(pharmacology)
- Blood Flow Velocity
- Capillaries
(metabolism, physiopathology)
- Carcinogens
(pharmacology)
- DNA
(metabolism)
- Disease Models, Animal
- Femoral Artery
(surgery)
- Hypoxia
(etiology, metabolism, physiopathology)
- Hypoxia-Inducible Factor 1, alpha Subunit
(genetics, metabolism)
- Ischemia
(complications, metabolism, physiopathology)
- Laser-Doppler Flowmetry
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Neovascularization, Physiologic
- Promoter Regions, Genetic
- RNA, Messenger
(metabolism)
- Receptor, Platelet-Derived Growth Factor beta
(metabolism)
- Receptors, Aryl Hydrocarbon
(deficiency, drug effects, genetics, metabolism)
- Receptors, Vascular Endothelial Growth Factor
(metabolism)
- Regional Blood Flow
- Time Factors
- Up-Regulation
- Vascular Endothelial Growth Factor A
(metabolism)
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