19351592

pubmed:Citation

1

We have investigated the effect of benzo[a]pyrene (B[a]P), a carcinogen of tobacco smoke and an agonist for the aryl hydrocarbon receptor (AHR), on hypoxia-induced angiogenesis. Ischemia was induced by femoral artery ligation in wild-type and AHR-null mice, and the animals were subjected to oral administration of B[a]P (125 mg/kg) once a week. Exposure to B[a]P up-regulated the expression of metallothionein in the ischemic hindlimb and markedly inhibited ischemia-induced angiogenesis in wild-type mice. The amounts of interleukin-6 and of vascular endothelial growth factor (VEGF) mRNA in the ischemic hindlimb of wild-type mice were reduced by exposure to B[a]P. These various effects of B[a]P were markedly attenuated in AHR-null mice. Our observations suggest that the loss of the inhibitory effect of B[a]P on ischemia-induced angiogenesis apparent in AHR-null mice may be attributable to maintenance of interleukin-6 expression and consequent promotion of angiogenesis through up-regulation of VEGF expression.

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http://linkedlifedata.com/resource/pubmed/journal/0372516

http://linkedlifedata.com/resource/pubmed/chemical/Angiotensin I, http://linkedlifedata.com/resource/pubmed/chemical/Arnt protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Aryl Hydrocarbon Receptor Nuclear..., http://linkedlifedata.com/resource/pubmed/chemical/Benzo(a)pyrene, http://linkedlifedata.com/resource/pubmed/chemical/Carcinogens, http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 CYP1A1, http://linkedlifedata.com/resource/pubmed/chemical/Hif1a protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha..., http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6, http://linkedlifedata.com/resource/pubmed/chemical/Metallothionein, http://linkedlifedata.com/resource/pubmed/chemical/Mt2 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Angiotensin, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Aryl Hydrocarbon, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Vascular Endothelial..., http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A, http://linkedlifedata.com/resource/pubmed/chemical/metallothionein-1, mouse

Mar

pubmed-author:GonzalezFrank JFJ, pubmed-author:IchiharaGakuG, pubmed-author:IchiharaSahokoS, pubmed-author:MuroharaToyoakiT, pubmed-author:NakajimaTamieT, pubmed-author:YamadaYoshijiY

27

NLM

44-9

pubmed-meshheading:19351592-Angiotensin I, pubmed-meshheading:19351592-Animals, pubmed-meshheading:19351592-Aryl Hydrocarbon Receptor Nuclear Translocator, pubmed-meshheading:19351592-Benzo(a)pyrene, pubmed-meshheading:19351592-Carcinogens, pubmed-meshheading:19351592-Cytochrome P-450 CYP1A1, pubmed-meshheading:19351592-Femoral Artery, pubmed-meshheading:19351592-Hypoxia-Inducible Factor 1, alpha Subunit, pubmed-meshheading:19351592-Interleukin-6, pubmed-meshheading:19351592-Ischemia, pubmed-meshheading:19351592-Lower Extremity, pubmed-meshheading:19351592-Male, pubmed-meshheading:19351592-Metallothionein, pubmed-meshheading:19351592-Mice, pubmed-meshheading:19351592-Mice, Inbred Strains, pubmed-meshheading:19351592-Neovascularization, Physiologic, pubmed-meshheading:19351592-Receptors, Angiotensin, pubmed-meshheading:19351592-Receptors, Aryl Hydrocarbon, pubmed-meshheading:19351592-Receptors, Vascular Endothelial Growth Factor, pubmed-meshheading:19351592-Up-Regulation, pubmed-meshheading:19351592-Vascular Endothelial Growth Factor A

Inhibition of ischemia-induced angiogenesis by benzo[a]pyrene in a manner dependent on the aryl hydrocarbon receptor.