{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T05:05:00Z","timestamp":1780463100962,"version":"3.54.1"},"reference-count":26,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T00:00:00Z","timestamp":1780185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Background: Carotid atherosclerosis and plaque instability are major drivers of ischemic stroke. The NLRP3 inflammasome and interleukin-1 (IL-1) pathway are recognized as key upstream regulators of atherogenesis. This systematic review aims to synthesize the available evidence regarding the impact of NLRP3 and IL-1-mediated inflammation on plaque vulnerability and clinical outcomes in patients undergoing carotid endarterectomy (CEA). Materials and Methods: A systematic search was performed relying on MEDLINE, Scopus, and Web of Science for studies assessing NLRP3 inflammasome and IL-1-mediated biomarkers in adult patients undergoing CEA. Data extraction and risk-of-bias evaluation were independently performed using the National Heart, Lung, and Blood Institute (NHLBI) Quality Assessment Tool. Due to substantial methodological heterogeneity, a narrative synthesis was conducted. Results: Sixteen studies involving 1677 participants were included. Evidence demonstrates that NLRP3 inflammasome components (NLRP3, ASC, Caspase-1) and IL-1 family cytokines (IL-1\u03b2, IL-18) are consistently elevated in unstable plaques and in symptomatic patients compared to asymptomatic counterparts. These markers were associated with histological features of instability, such as intraplaque haemorrhage, large lipid cores and extensive macrophage infiltration. While some data suggest a link between these biomarkers and Major Adverse Cardiovascular Events (MACE), most studies were limited by a lack of adjusted multivariable modelling and an overall unclear risk of bias. Conclusions: NLRP3\/IL-1\/-mediated inflammation is a promising biomarker axis for carotid plaque vulnerability and symptomatic disease. However, small, heterogeneous cohorts and limited adjusted analyses highlight the need for larger, well-designed studies to refine risk stratification and guide targeted anti-inflammatory strategies in carotid atherosclerosis.<\/jats:p>","DOI":"10.3390\/medsci14020280","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T17:11:01Z","timestamp":1780333861000},"page":"280","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["NLRP3 Inflammasome and IL-1\u2013Mediated Inflammation in Human Carotid Atherosclerosis: A Systematic Review of Endarterectomy-Based Evidence"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4109-3784","authenticated-orcid":false,"given":"David","family":"Mendon\u00e7a-Soares","sequence":"first","affiliation":[{"name":"Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ant\u00f3nia","family":"Rocha-Melo-Sousa","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"MEDCIDS\u2014Department of Community Medicine, Information and Health Decision Sciences, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7087-8674","authenticated-orcid":false,"given":"Mohammed","family":"Shahat","sequence":"additional","affiliation":[{"name":"Department of Vascular and Endovascular Surgery, Assiut University Hospitals, Assiut 2074020, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e1rmen","family":"Tavares","sequence":"additional","affiliation":[{"name":"Nova Medical School, 1169-056 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Institute of Anatomical and Molecular Pathology, Faculty of Medicine, University of Coimbra, 3000-370 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitor","family":"S\u00e1-Martins","sequence":"additional","affiliation":[{"name":"Nova Medical School, 1169-056 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Neiva-Sousa","sequence":"additional","affiliation":[{"name":"Functional Unit of Maxillofacial Surgery, Unidade Local de Sa\u00fade do Alto Ave (ULSAAVE), 4835-044 Guimar\u00e3es, Portugal"},{"name":"School of Medicine and Biomedical Sciences, Universidade Fernando Pessoa, 4420-096 Gondomar, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Frag\u00e3o-Marques","sequence":"additional","affiliation":[{"name":"Department of Imuno-Physiology and Pharmacology, Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS), Universidade do Porto, 4050-313 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2656-8935","authenticated-orcid":false,"given":"Jo\u00e3o Rocha","family":"Neves","sequence":"additional","affiliation":[{"name":"Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"RISE-Health, Departamento de Biomedicina, Faculdade de Medicina, Universidade do Porto, 4200-319 Porto, Portugal"},{"name":"Department of Vascular Surgery, Unidade Local de Sa\u00fade do Alto Ave (ULSAAVE), 4835-044 Guimar\u00e3es, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.ejvs.2022.04.011","article-title":"Editor\u2019s Choice\u2014European Society for Vascular Surgery (ESVS) 2023 Clinical Practice Guidelines on the Management of Atherosclerotic Carotid and Vertebral Artery Disease","volume":"65","author":"Naylor","year":"2023","journal-title":"Eur. 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