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While the molecular mechanisms underlying RT-induced cardiovascular damage remain unclear, the NLRP3 inflammasome has emerged as a central player in its pathogenesis. This review focuses on the current understanding of the involvement of NLRP3 in radiation-induced cardiotoxicity, highlighting emerging evidence reported in the literature. Recent findings shown that the NLRP3 inflammasome may play a role in radiation-induced cardiovascular diseases, drawing attention to it as a potential therapeutic target. We summarize key findings on the role of radiation in modulating the NLRP3 inflammasome and inducing cardiovascular disease, providing a detailed overview of NLRP3 inflammasome functions in different radiation-induced cardiovascular diseases. Moreover, we discuss the therapeutic potential of targeting NLRP3 to prevent radiation-induced cardiovascular diseases. The development of effective treatments for radiotherapy-induced cardiotoxicity is becoming increasingly urgent and understanding NLRP3-dependent mechanisms could pave the way for innovative therapeutic approaches.<\/jats:p>","DOI":"10.1186\/s12967-025-07377-3","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T14:17:19Z","timestamp":1763734639000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Radiation meets inflammation: NLRP3 inflammasome at the core of radiation-induced cardiac injury"],"prefix":"10.1186","volume":"23","author":[{"given":"Caterina","family":"Boncompagni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Giacovazzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariasole","family":"Perrone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Missiroli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio","family":"Righes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Pinton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2494-7405","authenticated-orcid":false,"given":"Carlotta","family":"Giorgi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,21]]},"reference":[{"key":"7377_CR1","doi-asserted-by":"publisher","first-page":"896","DOI":"10.3390\/jcm9040896","volume":"9","author":"R Kikuchi","year":"2020","unstructured":"Kikuchi R, Shah NP, Dent SF. 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