{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T08:08:24Z","timestamp":1790755704858,"version":"4.1.0"},"reference-count":35,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T00:00:00Z","timestamp":1694131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"National Research Agency (ANR)","doi-asserted-by":"publisher","award":["ANR-16-RHUS-0003"],"award-info":[{"award-number":["ANR-16-RHUS-0003"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"name":"GCS G4","award":["ANR-16-RHUS-0003"],"award-info":[{"award-number":["ANR-16-RHUS-0003"]}]},{"name":"Universit\u00e9 de Caen Normandie","award":["ANR-16-RHUS-0003"],"award-info":[{"award-number":["ANR-16-RHUS-0003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Thoracic radiation therapy may result in accelerated atherosclerosis and in late aortic valve stenosis (AS). In this study, we assessed the feasibility of inducing radiation-induced AS using a targeted aortic valve irradiation (10 or 20 Grays) in two groups of C57Bl6\/J (WT) and ApoE\u2212\/\u2212 mice compared to a control (no irradiation). Peak aortic jet velocity was evaluated by echocardiography to characterize AS. T2*-weighted magnetic resonance imaging after injection of MPIO-\u03b1VCAM-1 was used to examine aortic inflammation resulting from irradiation. A T2* signal void on valve leaflets and aortic sinus was considered positive. Valve remodeling and mineralization were assessed using von Kossa staining. Finally, the impact of radiation on cell viability and cycle from aortic human valvular interstitial cells (hVICs) was also assessed. The targeted aortic valve irradiation in ApoE\u2212\/\u2212 mice resulted in an AS characterized by an increase in peak aortic jet velocity associated with valve leaflet and aortic sinus remodeling, including mineralization process, at the 3-month follow-up. There was a linear correlation between histological findings and peak aortic jet velocity (r = 0.57, p &lt; 0.01). In addition, irradiation was associated with aortic root inflammation, evidenced by molecular MR imaging (p &lt; 0.01). No significant effect of radiation exposure was detected on WT animals. Radiation exposure did not affect hVICs viability and cell cycle. We conclude that targeted radiation exposure of the aortic valve in mice results in ApoE\u2212\/\u2212, but not in WT, mice in an aortic valve remodeling mimicking the human lesions. This preclinical model could be a useful tool for future assessment of therapeutic interventions.<\/jats:p>","DOI":"10.3390\/jcm12185854","type":"journal-article","created":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T09:11:18Z","timestamp":1694423478000},"page":"5854","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Targeted Radiation Exposure Induces Accelerated Aortic Valve Remodeling in ApoE\u2212\/\u2212 Mice"],"prefix":"10.3390","volume":"12","author":[{"given":"Guillaume","family":"Rucher","sequence":"first","affiliation":[{"name":"Normandie Univ, UNICAEN, UR 4650 PSIR, GIP Cyceron, 14000 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3234-5284","authenticated-orcid":false,"given":"Kevin","family":"Prigent","sequence":"additional","affiliation":[{"name":"Normandie Univ, UNICAEN, UR 4650 PSIR, GIP Cyceron, 14000 Caen, France"},{"name":"Department of Nuclear Medicine, CHU de Caen, 14000 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Simard","sequence":"additional","affiliation":[{"name":"Normandie Univ, UNICAEN, UR 4650 PSIR, GIP Cyceron, 14000 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0545-8577","authenticated-orcid":false,"given":"Anne-Marie","family":"Frelin","sequence":"additional","affiliation":[{"name":"Grand Acc\u00e9l\u00e9rateur National d\u2019Ions Lourds (GANIL), CEA\/DRF-CNRS\/IN2P3, 14000 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u00eblle","family":"Coquemont-Guyot","sequence":"additional","affiliation":[{"name":"Normandie Univ, UNICAEN, SF 4207, PLATON Services Unit, Virtual\u2019His, 14000 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5772-8252","authenticated-orcid":false,"given":"Nicolas","family":"Elie","sequence":"additional","affiliation":[{"name":"Normandie Univ, UNICAEN, SF 4207, PLATON Services Unit, Virtual\u2019His, 14000 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Delcroix","sequence":"additional","affiliation":[{"name":"CNRS, UMS-3048, GIP Cyceron, Campus Jules Horowitz, 14000 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0854-1931","authenticated-orcid":false,"given":"Nicolas","family":"Perzo","sequence":"additional","affiliation":[{"name":"Normandie Univ, UNIROUEN, INSERM U1096 EnVI, 76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Guinamard","sequence":"additional","affiliation":[{"name":"Normandie Univ, UNICAEN, UR 4650 PSIR, GIP Cyceron, 14000 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludovic","family":"Berger","sequence":"additional","affiliation":[{"name":"Normandie Univ, UNICAEN, UR 4650 PSIR, GIP Cyceron, 14000 Caen, France"},{"name":"Department of Vascular Surgery, Normandie Univ, UNICAEN, UR 4650 PSIR, CHU de Caen, 14000 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1578-0922","authenticated-orcid":false,"given":"Alain","family":"Manrique","sequence":"additional","affiliation":[{"name":"Normandie Univ, UNICAEN, UR 4650 PSIR, GIP Cyceron, 14000 Caen, France"},{"name":"Department of Nuclear Medicine, CHU de Caen, 14000 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the STOP-AS Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e021686","DOI":"10.1161\/JAHA.121.021686","article-title":"Radiation-Induced Cardiovascular Disease: Review of an Underrecognized Pathology","volume":"10","author":"Eisenberg","year":"2021","journal-title":"J. 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