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タイトル: | Irradiation Accelerates Plaque Formation and Cellular Senescence in Flow‐Altered Carotid Arteries of Apolipoprotein E Knock‐Out Mice |
著者: | Yamamoto, Yu Minami, Manabu Yoshida, Kazumichi ![]() ![]() Nagata, Manabu Miyata, Takeshi Yang, Tao Takayama, Naoki Suzuki, Keita Okawa, Masakazu Yamada, Kiyofumi Miyamoto, Susumu |
著者名の別形: | 山本, 優 南, 学 吉田, 和道 永田, 学 宮田, 武 楊, 涛 高山, 直樹 鈴木, 啓太 大川, 将和 山田, 清文 宮本, 享 |
キーワード: | carotid artery stenosis irradiation atherosclerosis DNA damage cellular senescence |
発行日: | Jul-2021 |
出版者: | American Heart Association |
誌名: | Journal of the American Heart Association |
巻: | 10 |
号: | 14 |
論文番号: | e020712 |
抄録: | [Background] Chronic inflammation through cellular senescence, known as the senescence‐associated secretory phenotype, is a mechanism of various organ diseases, including atherosclerosis. Particularly, ionizing radiation (IR) contributes to cellular senescence by causing DNA damage. Although previous clinical studies have demonstrated that radiotherapy causes atherosclerosis as a long‐term side effect, the detailed mechanism is unclear. This study was conducted to investigate the relationship between radiation‐induced atherosclerosis and senescence‐associated secretory phenotype in murine carotid arteries. [Methods and Results] Partial ligation of the left carotid artery branches in 9‐week‐old male apolipoprotein E‐deficient mice was performed to induce atherosclerosis. The mice received total body irradiation at a dose of 6 Gy using gamma rays at 2 weeks post operation. We compared the samples collected 4 weeks after IR with unirradiated control samples. The IR and control groups presented pathologically progressive lesions in 90.9% and 72.3% of mice, respectively. Plaque volume, macrophage accumulation, and phenotype switching of vascular smooth muscle cells were advanced in the IR group. Irradiated samples showed increased persistent DNA damage response (53BP1 [p53 binding protein 1]), upregulated cyclin‐dependent kinase inhibitors (p16INK4a and p21), and elevated inflammatory chemokines expression (monocyte chemotactic protein‐1, keratinocyte‐derived chemokine, and macrophage inflammatory protein 2). [Conclusions] IR promoted plaque growth in murine carotid arteries. Our findings support the possibility that senescence‐associated secretory phenotype aggravates atherogenesis in irradiated artery. This mice model might contribute to mechanism elucidation of radiation‐induced atherosclerosis. |
著作権等: | Copyright © 2021 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
URI: | http://hdl.handle.net/2433/277887 |
DOI(出版社版): | 10.1161/JAHA.120.020712 |
PubMed ID: | 34227406 |
出現コレクション: | 学術雑誌掲載論文等 |
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