{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T07:03:24Z","timestamp":1782975804000,"version":"3.54.5"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Radiation-induced heart injury (RIHI) is a major late toxicity of thoracic radiotherapy, yet the cellular and molecular mechanisms driving its progression remain poorly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Single-cell RNA sequencing (scRNA-seq) was performed on rat hearts and matched peripheral blood mononuclear cells (PBMCs) 12 weeks after whole-heart irradiation (20\u2005Gy) or sham control, profiling 38,941 cardiac cells across 15 types and 41,097 PBMCs across 9 types. Differential expression, pathway enrichment, pseudotime, and ligand\u2013receptor interaction analyses were conducted. Key findings in endothelial cells and fibroblasts were validated by Western blotting and flow cytometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Major cardiac populations, including cardiomyocytes, endothelial cells (ECs), fibroblasts, neutrophils, macrophages, T cells, NK cells, and B cells, were defined in control and RIHI hearts. Following irradiation, ECs showed distinct subtype shifts with marked MHC-II upregulation, while fibroblasts exhibited iron accumulation, pro-inflammatory activation, and antigen-presenting properties. These stromal alterations coincided with myeloid activation (macrophage and IL-1\u03b2\u207a neutrophil programs) and T\/NK cell polarization toward cytotoxic yet partially exhausted states, together with enhanced B-cell antigen presentation. Collectively, these findings delineate a stromal\u2013immune cascade linking radiation injury to chronic cardiac inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>RIHI progresses through a stromal-immune cascade where EC and fibroblast immunogenic reprogramming initiates sustained myeloid and lymphoid activation, creating a pro-inflammatory cardiac microenvironment. These findings highlight non-hematopoietic antigen presentation as a therapeutic target in thoracic radiotherapy, particularly when combined with immune checkpoint inhibitors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2026.1836858","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T05:35:55Z","timestamp":1782970555000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Immune and stromal remodeling underlies radiation-induced heart injury: insights from single-cell transcriptomics"],"prefix":"10.3389","volume":"13","author":[{"given":"Xia","family":"Yan","sequence":"first","affiliation":[{"name":"Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital","place":["Taiyuan, Shanxi, China"]},{"name":"Shanxi Provincial Key Laboratory for Translational Nuclear Medicine and Precision Protection","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JiaYi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital","place":["Taiyuan, Shanxi, China"]},{"name":"Shanxi Provincial Key Laboratory for Translational Nuclear Medicine and Precision Protection","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"QinYing","family":"Shi","sequence":"additional","affiliation":[{"name":"Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital","place":["Taiyuan, Shanxi, China"]},{"name":"Shanxi Provincial Key Laboratory for Translational Nuclear Medicine and Precision Protection","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Yan","sequence":"additional","affiliation":[{"name":"Nursing College of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, First Hospital of Shanxi Medical University, Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianbo","family":"Song","sequence":"additional","affiliation":[{"name":"Shanxi Provincial People\u2019s Hospital Affiliated to Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.2147\/IJN.S290438","article-title":"Application of radiosensitizers in cancer radiotherapy","volume":"16","author":"Gong","year":"2021","journal-title":"Int J Nanomedicine"},{"key":"B2","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1093\/pcmedi\/pbz025","article-title":"Radiotherapy-induced heart disease: a review of the literature","volume":"2","author":"Zou","year":"2019","journal-title":"Precis Clin Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1001\/jamaoncol.2020.7468","article-title":"Association of breast cancer irradiation with cardiac toxic effects: a narrative review","volume":"7","author":"Meattini","year":"2021","journal-title":"JAMA Oncol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"e108","DOI":"10.1016\/S1470-2045(23)00012-8","article-title":"Systematic review and updated recommendations for cardiomyopathy surveillance for survivors of childhood, adolescent, and young adult cancer from the international late effects of childhood cancer guideline harmonization group","volume":"24","author":"Ehrhardt","year":"2023","journal-title":"Lancet Oncol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2084","DOI":"10.1002\/ejhf.3753","article-title":"Prevention of cancer therapy-related cardiac dysfunction and heart failure in cancer patients and survivors. 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