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NLRP3 (NLR family pyrin domain containing 3) inflammasome, as a critical component of the innate immune system, plays a pivotal role in the inflammatory response. Many research studies have highlighted the implication of NLRP3 in the pathogenesis of various cardiovascular diseases including atherosclerosis, myocardial infarction, hypertension and heart failure. Activation of NLRP3 elicits a robust inflammatory response represented in proteolytic cleavage and release of pro\u2010inflammatory cytokines such as IL\u20101\u03b2 and IL\u201018, which contribute to the progression of vascular inflammation and myocardial damage. This narrative review aims to comprehensively summarize the current evidence of NLRP3 inflammasome activation in cardiovascular diseases, elucidate the underlying molecular mechanisms, and critically evaluate emerging NLRP3 inhibitors. Particular emphasis is placed on novel synthetic small\u2010molecule inhibitors and bioactive phytoestrogens targeting NLRP3 as potential therapeutic strategies. Collectively, targeting NLRP3 represents a new frontier in cardiovascular disease management. However, further research is needed to optimize these compounds in preclinical models and to explore their efficacy and safety in human studies, paving the way for innovative treatments that could transform the management of cardiovascular diseases.<\/jats:p>","DOI":"10.1002\/ddr.70283","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T09:53:37Z","timestamp":1775814817000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting the NLRP3 Inflammasome: Novel Inhibitors for Cardiovascular Diseases Management \u2014 A Narrative Review"],"prefix":"10.1002","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8280-8959","authenticated-orcid":false,"given":"Yomna S.","family":"Momen","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy Beni\u2010Suef University Beni\u2010Suef Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1230751"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.9b00138"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv318"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00380-015-0723-8"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2020.127571"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.9b00433"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26123534"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-39805-z"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.11.011"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci25495"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1590\/s0102-865020190110000004"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.26355\/eurrev_201911_19579"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2017.08.011"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201700731"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2018.11.013"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.879021"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.202201494"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.550624"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-022-04120-2"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-012414-040431"},{"key":"e_1_2_14_22_1","unstructured":"Brough D. 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