title: Irradiation induces different inflammatory and thrombotic responses in carotid arteries of wildtype C57BL/6J and atherosclerosis-prone ApoE(-/-) mice.
abstract: OBJECTIVE
  We have previously shown that irradiation to the carotid arteries of hypercholesterolemic ApoE(-/-) mice accelerated the development of macrophage-rich, inflammatory atherosclerotic lesions. We now investigated the mechanism underlying the development of radiation-induced atherosclerosis.
  
  
  METHODS
  ApoE(-/-) and wildtype C57BL/6J mice received 0, 8 or 14 Gy to the neck and the carotid arteries were harvested 1 day, 1 or 4 weeks later. Immunohistochemical stainings were performed to evaluate well-known inflammatory and thrombotic molecules. A hypothesis-generating approach was used to compare gene expression profiles of irradiated and unirradiated carotid arteries.
  
  
  RESULTS
  Basal levels of endothelial VCAM-1 and thrombomodulin immunoexpression were higher in ApoE(-/-) mice than in C57BL/6J mice. At 1 week after 14 Gy VCAM-1 immunoexpression was decreased in ApoE(-/-) mice, whereas ICAM-1 immunoexpression was decreased at 1 and 4 weeks after 14 Gy in C57BL/6J mice. Thrombomodulin and tissue factor immunoexpression were elevated at 4 weeks after 14 Gy in ApoE(-/-) mice and reduced in C57BL/6J mice. There were no changes in immunoexpression of eNOS, MCP-1 or endoglin. Several canonical pathways were differentially expressed after irradiation, including tight junction pathways, leukocyte extravasation signaling and PI3K/AKT signaling.
  
  
  CONCLUSIONS
  ApoE(-/-) and C57BL/6J mice respond differently to irradiation. The thrombotic pathways were activated after irradiation in ApoE(-/-) mice only. Genes involved in tight junction regulation were up-regulated in ApoE(-/-) mice and decreased in C57BL/6J mice. These factors may have contributed to fatty-streak formation in ApoE(-/-) mice.
authors.affiliation: The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Saske
authors.initials: S
authors.lastname: Hoving
authors.forename: Sylvia
authors.initials: S
authors.lastname: Heeneman
authors.forename: Marion J J
authors.initials: MJ
authors.lastname: Gijbels
authors.forename: Johannes A M
authors.initials: JA
authors.lastname: Te Poele
authors.forename: Nils
authors.initials: N
authors.lastname: Visser
authors.forename: Jack
authors.initials: J
authors.lastname: Cleutjens
authors.forename: Nicola S
authors.initials: NS
authors.lastname: Russell
authors.forename: Mat J A P
authors.initials: MJ
authors.lastname: Daemen
authors.forename: Fiona A
authors.initials: FA
authors.lastname: Stewart
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D050197:Atherosclerosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002339:Carotid Arteries / Q000473:pathology / Q000528:radiation effects*; D004730:Endothelium, Vascular / Q000473:pathology / Q000528:radiation effects*; D005260:Female; D015870:Gene Expression; D007249:Inflammation / Q000209:etiology / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009333:Neck / Q000528:radiation effects; D011833:Radiation Injuries, Experimental / Q000473:pathology; D011897:Random Allocation; D018180:Thrombomodulin / Q000378:metabolism; D013927:Thrombosis / Q000209:etiology* / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D001057:Apolipoproteins E; D018180:Thrombomodulin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1