TY - JOUR
T1 - Irradiation induces different inflammatory and thrombotic responses in carotid arteries of wildtype C57BL/6J and atherosclerosis-prone ApoE(-/-) mice
AU - Hoving, Saske
AU - Heeneman, Sylvia
AU - Gijbels, Marion J. J.
AU - te Poele, Johannes A. M.
AU - Visser, Nils
AU - Cleutjens, Jack
AU - Russell, Nicola S.
AU - Daemen, Mat J. A. P.
AU - Stewart, Fiona A.
PY - 2012
Y1 - 2012
N2 - Background and purpose: 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. Materials and 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/61 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. Conclusion: 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. (C) 2012 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 105 (2012) 365-370
AB - Background and purpose: 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. Materials and 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/61 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. Conclusion: 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. (C) 2012 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 105 (2012) 365-370
U2 - https://doi.org/10.1016/j.radonc.2012.11.001
DO - https://doi.org/10.1016/j.radonc.2012.11.001
M3 - Article
C2 - 23245647
SN - 0167-8140
VL - 105
SP - 365
EP - 370
JO - Radiotherapy and oncology
JF - Radiotherapy and oncology
IS - 3
ER -