{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T19:55:51Z","timestamp":1780343751253,"version":"3.54.1"},"reference-count":85,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T00:00:00Z","timestamp":1616457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AAI-12044-001-04000"],"award-info":[{"award-number":["AAI-12044-001-04000"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Clinical, epidemiological, and experimental evidence demonstrate non-cancer, cardiovascular, and endocrine effects of ionizing radiation exposure including growth hormone deficiency, obesity, metabolic syndrome, diabetes, and hyperinsulinemia. Insulin-like growth factor-1 (IGF-1) signaling perturbations are implicated in development of cardiovascular disease and metabolic syndrome. The minipig is an emerging model for studying radiation effects given its high analogy to human anatomy and physiology. Here we use a minipig model to study late health effects of radiation by exposing male G\u00f6ttingen minipigs to 1.9\u20132.0 Gy X-rays (lower limb tibias spared). Animals were monitored for 120 days following irradiation and blood counts, body weight, heart rate, clinical chemistry parameters, and circulating biomarkers were assessed longitudinally. Collagen deposition, histolopathology, IGF-1 signaling, and mRNA sequencing were evaluated in tissues. Our findings indicate a single exposure induced histopathological changes, attenuated circulating IGF-1, and disrupted cardiac IGF-1 signaling. Electrolytes, lipid profiles, liver and kidney markers, and heart rate and rhythm were also affected. In the heart, collagen deposition was significantly increased and transforming growth factor beta-1 (TGF-beta-1) was induced following irradiation; collagen deposition and fibrosis were also observed in the kidney of irradiated animals. Our findings show G\u00f6ttingen minipigs are a suitable large animal model to study long-term effects of radiation exposure and radiation-induced inhibition of IGF-1 signaling may play a role in development of late organ injuries.<\/jats:p>","DOI":"10.3390\/ijms22063286","type":"journal-article","created":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T14:08:16Z","timestamp":1616508496000},"page":"3286","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Late Health Effects of Partial Body Irradiation Injury in a Minipig Model Are Associated with Changes in Systemic and Cardiac IGF-1 Signaling"],"prefix":"10.3390","volume":"22","author":[{"given":"Bernadette","family":"Hritzo","sequence":"first","affiliation":[{"name":"Armed Forces Radiobiology Research Institute, Bethesda, MD 20889, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeed Y.","family":"Aghdam","sequence":"additional","affiliation":[{"name":"Armed Forces Radiobiology Research Institute, Bethesda, MD 20889, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betre","family":"Legesse","sequence":"additional","affiliation":[{"name":"Armed Forces Radiobiology Research Institute, Bethesda, MD 20889, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amandeep","family":"Kaur","sequence":"additional","affiliation":[{"name":"Armed Forces Radiobiology Research Institute, Bethesda, MD 20889, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maohua","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Endodontics, Texas A&amp;M College of Dentistry, Dallas, TX 75246, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2249-5203","authenticated-orcid":false,"given":"Marjan","family":"Boerma","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR 72205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabarun","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Medical Readiness Systems Biology, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"},{"name":"The Geneva Foundation, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Dimitrov","sequence":"additional","affiliation":[{"name":"Medical Readiness Systems Biology, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"},{"name":"The Geneva Foundation, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aarti","family":"Gautam","sequence":"additional","affiliation":[{"name":"The Geneva Foundation, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasha","family":"Hammamieh","sequence":"additional","affiliation":[{"name":"The Geneva Foundation, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Wilkins","sequence":"additional","affiliation":[{"name":"Armed Forces Radiobiology Research Institute, Bethesda, MD 20889, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alena","family":"Tsioplaya","sequence":"additional","affiliation":[{"name":"Armed Forces Radiobiology Research Institute, Bethesda, MD 20889, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory P.","family":"Holmes-Hampton","sequence":"additional","affiliation":[{"name":"Armed Forces Radiobiology Research Institute, Bethesda, MD 20889, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Moroni","sequence":"additional","affiliation":[{"name":"Armed Forces Radiobiology Research Institute, Bethesda, MD 20889, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S122","DOI":"10.1001\/dmp.2011.21","article-title":"Long-term radiation-related health effects in a unique human population: Lessons learned from the atomic bomb survivors of Hiroshima and Nagasaki","volume":"5","author":"Douple","year":"2011","journal-title":"Disaster Med. 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