{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:58:25Z","timestamp":1790740705807,"version":"4.1.0"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"14","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,7,20]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Chronic inflammation through cellular senescence, known as the senescence\u2010associated 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\u2010term side effect, the detailed mechanism is unclear. This study was conducted to investigate the relationship between radiation\u2010induced atherosclerosis and senescence\u2010associated secretory phenotype in murine carotid arteries.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">Partial ligation of the left carotid artery branches in 9\u2010week\u2010old male apolipoprotein E\u2010deficient mice was performed to induce atherosclerosis. The mice received total body irradiation at a dose of 6\u00a0Gy using gamma rays at 2\u00a0weeks post operation. We compared the samples collected 4\u00a0weeks 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\u2010dependent kinase inhibitors (p16INK4a and p21), and elevated inflammatory chemokines expression (monocyte chemotactic protein\u20101, keratinocyte\u2010derived chemokine, and macrophage inflammatory protein 2).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">IR promoted plaque growth in murine carotid arteries. Our findings support the possibility that senescence\u2010associated secretory phenotype aggravates atherogenesis in irradiated artery. This mice model might contribute to mechanism elucidation of radiation\u2010induced atherosclerosis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.120.020712","type":"journal-article","created":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T09:54:06Z","timestamp":1625565246000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":23,"title":["Irradiation Accelerates Plaque Formation and Cellular Senescence in Flow\u2010Altered Carotid Arteries of Apolipoprotein E Knock\u2010Out Mice"],"prefix":"10.1161","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8580-0589","authenticated-orcid":false,"given":"Yu","family":"Yamamoto","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Kyoto University Graduate School of Medicine Kyoto Japan"},{"name":"Department of Clinical Innovative Medicine Kyoto University Graduate School of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0052-398X","authenticated-orcid":false,"given":"Manabu","family":"Minami","sequence":"additional","affiliation":[{"name":"Department of Clinical Innovative Medicine Kyoto University Graduate School of Medicine Kyoto Japan"},{"name":"Department of Data Science National Cerebral and Cardiovascular Center Suita Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8898-079X","authenticated-orcid":false,"given":"Kazumichi","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Kyoto University Graduate School of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1288-5526","authenticated-orcid":false,"given":"Manabu","family":"Nagata","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Kyoto University Graduate School of Medicine Kyoto Japan"},{"name":"Department of Clinical Innovative Medicine Kyoto University Graduate School of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Miyata","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Kyoto University Graduate School of Medicine Kyoto Japan"},{"name":"Department of Clinical Innovative Medicine Kyoto University Graduate School of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Kyoto University Graduate School of Medicine Kyoto Japan"},{"name":"Department of Clinical Innovative Medicine Kyoto University Graduate School of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2352-9532","authenticated-orcid":false,"given":"Naoki","family":"Takayama","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Kyoto University Graduate School of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keita","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Kyoto University Graduate School of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masakazu","family":"Okawa","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Kyoto University Graduate School of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8869-6628","authenticated-orcid":false,"given":"Kiyofumi","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Kyoto University Graduate School of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susumu","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Kyoto University Graduate School of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz766"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1209825"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2008.12.019"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.111.615203"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2018.11.013"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4000"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1909"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.071340"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-34893-8"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000026393.47805.21"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf6659"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00510.2009"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.20.5.1262"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00381.2005"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/cm.1027"},{"key":"e_1_3_1_17_2","first-page":"305","article-title":"Gamma\u2010H2AX\u2014a novel biomarker for DNA double\u2010strand breaks","volume":"22","author":"Kuo LJ","year":"2008","unstructured":"Kuo LJ, Yang LX. Gamma\u2010H2AX\u2014a novel biomarker for DNA double\u2010strand breaks. In Vivo. 2008;22:305\u2013309.","journal-title":"In Vivo"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.5.1719-1729.2001"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.24.13742"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.3.2109"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2008.02.031"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2006.050409"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1080\/09553002.2017.1332438"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1097\/HP.0b013e318266ee13"},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0161079"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2010.00567.x"},{"key":"e_1_3_1_27_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2006.060116"},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.722355"},{"key":"e_1_3_1_29_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.110.209692"},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2012.00795.x"},{"key":"e_1_3_1_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2784"},{"key":"e_1_3_1_32_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.111.236349"},{"key":"e_1_3_1_33_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.115.305896"},{"key":"e_1_3_1_34_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.016457"},{"key":"e_1_3_1_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2015.03.021"},{"key":"e_1_3_1_36_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-04-1418"},{"key":"e_1_3_1_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3733"},{"key":"e_1_3_1_38_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.034392"},{"key":"e_1_3_1_39_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1701719"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.120.020712","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T11:22:21Z","timestamp":1715599341000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.120.020712"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,20]]},"references-count":38,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2021,7,20]]}},"alternative-id":["10.1161\/JAHA.120.020712"],"URL":"https:\/\/doi.org\/10.1161\/jaha.120.020712","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,20]]},"assertion":[{"value":"2020-12-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e020712"}}