{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:33:46Z","timestamp":1789558426699,"version":"build-2803163510"},"reference-count":56,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,8,31]],"date-time":"2024-08-31T00:00:00Z","timestamp":1725062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Recent epidemiological studies have shown that patients with right-sided breast cancer (RBC) treated with X-ray irradiation (IR) are more susceptible to developing cardiovascular diseases, such as arrhythmias, atrial fibrillation, and conduction disturbances after radiotherapy (RT). Our aim was to investigate the mechanisms induced by low to moderate doses of IR and to evaluate changes in the cardiac sympathetic nervous system (CSNS), atrial remodeling, and calcium homeostasis involved in cardiac rhythm. To mimic the RT of the RBC, female C57Bl\/6J mice were exposed to X-ray doses ranging from 0.25 to 2 Gy targeting 40% of the top of the heart. At 60 weeks after RI, Doppler ultrasound showed a significant reduction in myocardial strain, ejection fraction, and atrial function, with a significant accumulation of fibrosis in the epicardial layer and apoptosis at 0.5 mGy. Calcium transient protein expression levels, such as RYR2, NAK, Kir2.1, and SERCA2a, increased in the atrium only at 0.5 Gy and 2 Gy at 24 h, and persisted over time. Interestingly, 3D imaging of the cleaned hearts showed an early reduction of CSNS spines and dendrites in the ventricles and a late reorientation of nerve fibers, combined with a decrease in SEMA3a expression levels. Our results showed that local heart IR from 0.25 Gy induced late cardiac and atrial dysfunction and fibrosis development. After IR, ventricular CSNS and calcium transient protein expression levels were rearranged, which affected cardiac contractility. The results are very promising in terms of identifying pro-arrhythmic mechanisms and preventing arrhythmias during RT treatment in patients with RBC.<\/jats:p>","DOI":"10.3390\/ijms25179483","type":"journal-article","created":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T09:56:42Z","timestamp":1725357402000},"page":"9483","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["X-ray Radiotherapy Impacts Cardiac Dysfunction by Modulating the Sympathetic Nervous System and Calcium Transients"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3705-784X","authenticated-orcid":false,"given":"Justyne","family":"Feat-Vetel","sequence":"first","affiliation":[{"name":"Laboratoire de Pharmacologie Exp\u00e9rimentale et Mol\u00e9culaire (LPEM), Service d\u2019Ing\u00e9nierie Mol\u00e9culaire Pour la Sant\u00e9 (SIMoS), D\u00e9partement M\u00e9dicaments et Technologies Pour la Sant\u00e9 (DMTS), CEA, 91191 Gif-sur-Yvette, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9277-5089","authenticated-orcid":false,"given":"Nadine","family":"Suffee","sequence":"additional","affiliation":[{"name":"UMR 1166, Unit\u00e9 de Recherche sur les Maladies Cardiovasculaires et M\u00e9taboliques, INSERM, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Bachelot","sequence":"additional","affiliation":[{"name":"PSE-SANTE\/SESANE\/LRTOX, Institut de Radioprotection et de S\u00fbret\u00e9 Nucl\u00e9aire-IRSN, 92260 Fontenay-aux-Roses, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgane","family":"Dos Santos","sequence":"additional","affiliation":[{"name":"PSE-SANTE\/SERAMED\/LRAcc, Institut de Radioprotection et de S\u00fbret\u00e9 Nucl\u00e9aire-IRSN, 92260 Fontenay-aux-Roses, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Mougenot","sequence":"additional","affiliation":[{"name":"UMS28, INSERM, Sorbonne Universit\u00e9, Plateforme PECMV, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1217-6225","authenticated-orcid":false,"given":"Elise","family":"Delage","sequence":"additional","affiliation":[{"name":"CellTechs Laboratory, SupBiotech, 94800 Villejuif, France"},{"name":"Service d\u2019Etude des Prions et des Infections Atypiques, Institut Fran\u00e7ois Jacob, Commissariat \u00e0 l\u2019Energie Atomique et aux Energies Alternatives, Universit\u00e9 Paris Saclay, 91405 Fontenay-aux-Roses, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Saliou","sequence":"additional","affiliation":[{"name":"PSE-SANTE\/SESANE\/LRTOX, Institut de Radioprotection et de S\u00fbret\u00e9 Nucl\u00e9aire-IRSN, 92260 Fontenay-aux-Roses, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Martin","sequence":"additional","affiliation":[{"name":"Center for Interdisciplinary Research in Biology (CIRB), College de France, 75001 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Brunet","sequence":"additional","affiliation":[{"name":"Center for Interdisciplinary Research in Biology (CIRB), College de France, 75001 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5837-3916","authenticated-orcid":false,"given":"Pierre","family":"Sicard","sequence":"additional","affiliation":[{"name":"PhyMedExp, IPAM\/Biocampus, INSERM, CNRS, Universit\u00e9 de Montpellier, 34095 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1717-8935","authenticated-orcid":false,"given":"Virginie","family":"Monceau","sequence":"additional","affiliation":[{"name":"PSE-SANTE\/SESANE\/LRTOX, Institut de Radioprotection et de S\u00fbret\u00e9 Nucl\u00e9aire-IRSN, 92260 Fontenay-aux-Roses, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1667\/RR1789.1","article-title":"Cardiovascular diseases in the cohort of workers first employed at Mayak PA in 1948\u20131958","volume":"174","author":"Azizova","year":"2010","journal-title":"Radiat. 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