Single-dose and fractionated irradiation promote initiation and progression of atherosclerosis and induce an inflammatory plaque phenotype in ApoE-/- mice
Single-dose and fractionated irradiation promote initiation and progression of atherosclerosis and induce an inflammatory plaque phenotype in ApoE-/- mice
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DOI：
10.1016/j.ijrobp.2008.02.031
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发表时间：
2008-07-01
影响因子：
7
通讯作者：
Stewart, Fiona A.
中科院分区：
文献类型：
--
作者：
Hoving, Saske;Heeneman, Sylvia;Stewart, Fiona A.
Purpose: Increased risk of atherosclerosis and stroke has been demonstrated in patients receiving radiotherapy for Hodgkin's lymphoma and head-and-neck cancer. We previously showed that 14 Gy to the carotid arteries of hypercholesterolemic ApoE(-/-) mice resulted in accelerated development of macrophage-rich, inflammatory atherosclerotic lesions. Here we investigate whether clinically relevant fractionated irradiation schedules and lower single doses also predispose to an inflammatory plaque phenotype.Methods and Materials: ApoE(-/-) mice were given 8 or 14 Gy, or 20 x 2.0 Gy in 4 weeks to the neck, and the carotid arteries were subsequently examinated for presence of atherosclerotic lesions, plaque size, and phenotype.Results: At 4 weeks, early atherosclerotic lesions were found in 44% of the mice after single doses of 14 Gy but not in age-matched controls. At 22 to 30 weeks after irradiation there was a twofold increase in the mean number of carotid lesions (8-14 Gy and 20 x 2.0 Gy) and total plaque burden (single doses only), compared with age-matched controls. The majority of lesions seen at 30 to 34 weeks after fractionated irradiation or 14-Gy single doses were granulocyte rich (100% and 63%, respectively), with thrombotic features (90% and 88%), whereas these phenotypes were much less common in age-matched controls or after a single dose of 8 Gy.Conclusions: We showed that fractionated irradiation accelerated the development of atherosclerosis in ApoE(-/-) mice and predisposed to the formation of an inflammatory, thrombotic plaque phenotype. (C) 2008 Elsevier Inc.
