{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T19:13:11Z","timestamp":1793041991303,"version":"4.5.0"},"reference-count":136,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research (ICMR), India","doi-asserted-by":"publisher","award":["EMDR\/SG\/12\/2024\u201302666"],"award-info":[{"award-number":["EMDR\/SG\/12\/2024\u201302666"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]},{"award":["EMDR\/SG\/12\/2024\u201302666"],"award-info":[{"award-number":["EMDR\/SG\/12\/2024\u201302666"]}],"id":[{"id":"https:\/\/ror.org\/0492wrx28","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Endothelial dysfunction (ED) is an early event in cardiovascular and metabolic diseases, including atherosclerosis, diabetes, and hypertension. Emerging evidence highlights the interplay between chronic inflammation and oxidative stress, collectively termed OxInflammation, as a major driver of vascular injury and impaired tissue repair. Among the key mediators of this response is the Nod like receptor family pyrin domain containing 3 (NLRP3) inflammasome, a multiprotein complex that promotes the release of inflammatory cytokines, including Interleukin 1\u03b2 (IL-1\u03b2) and Interleukin-18 (IL-18), and induces gasdermin D-mediated pyroptotic cell death. Activation of NLRP3 disrupts endothelial function, reduces nitric oxide availability, and accelerates vascular inflammation and injury. This review discusses current evidence on pharmacological strategies targeting NLRP3 inflammasome signaling using both natural and synthetic inhibitors. Studies have shown that inhibiting NLRP3 can reduce inflammation and oxidative stress, preserve endothelial integrity, improve vascular function, and support tissue repair. Several NLRP3-targeting compounds have advanced into early-phase clinical trials, showing encouraging safety profiles and efficacy in individuals with cardiovascular risk factors. By integrating the emerging concept of OxInflammation with endothelial dysfunction, this review critically evaluates the therapeutic and translational potential of NLRP3 inflammasome inhibition in cardiovascular and metabolic disorders. Collectively, the available evidence supports NLRP3 as a promising therapeutic target for restoring endothelial homeostasis and promoting vascular repair. However, further clinical studies are needed to establish long-term efficacy, optimal dosing strategies, and appropriate patient selection criteria.<\/jats:p>","DOI":"10.3390\/antiox15070784","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:52:11Z","timestamp":1782453131000},"page":"784","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Role of NLRP3 Inflammasome Inhibitors in Endothelial Dysfunction and Vascular Repair"],"prefix":"10.3390","volume":"15","author":[{"given":"Thangasrinivasan","family":"Samyuktha","sequence":"first","affiliation":[{"name":"Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sridharan","family":"Yukta","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3198-6066","authenticated-orcid":false,"given":"Kumar","family":"Ganesan","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5450-902X","authenticated-orcid":false,"given":"Kunka Mohanram","family":"Ramkumar","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1210\/edrv.22.1.0417","article-title":"Diabetes and Endothelial Dysfunction: A Clinical Perspective","volume":"22","author":"Cipolla","year":"2001","journal-title":"Endocr. 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