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/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.
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.
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