{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T07:52:26Z","timestamp":1773388346752,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100014384","name":"Amarin Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014384","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabet Med"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Despite intensive lipid\u2010lowering therapy, individuals with atherosclerotic cardiovascular disease (ASCVD) exhibit residual inflammatory risk, which drives recurrent cardiovascular events. This risk is amplified in type 2 diabetes mellitus (T2DM), where a pro\u2010inflammatory milieu accelerates atherogenesis. Monocyte\u2010derived macrophages (MDMs), key mediators of vascular inflammation, contribute significantly to this process. Icosapent ethyl (IPE), a highly purified ethyl ester of eicosapentaenoic acid (EPA), reduces major adverse cardiovascular events (MACE) beyond triglyceride lowering, yet its cellular mechanisms remain unclear. This study aims to determine whether IPE modulates inflammatory pathways in patient\u2010derived MDMs and to distinguish direct EPA effects from therapy\u2010mediated changes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This single\u2010centre, open\u2010label, randomised observational cohort study will recruit ASCVD patients, stratified by T2DM status, who are prescribed IPE (Vazkepa\u00ae). MDMs and plasma\/serum samples will be collected from patients, either IPE\u2010na\u00efve or following 6\u2009months of therapy. In parallel, direct EPA effects will be assessed by treating MDMs from healthy donors and ASCVD patients with physiologically relevant concentrations of EPA. We will evaluate NOD\u2010like receptor protein 3 (NLRP3) inflammasome priming and activation, inflammatory cytokine profiles, and markers of cellular senescence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The study will investigate mechanisms that potentially underlie the cardiovascular benefits of IPE, focusing on the modulation of inflammatory pathways. We hypothesise that IPE attenuates priming and activation of the NLRP3 inflammasome in monocyte\u2010derived macrophages, thereby reducing cellular inflammation and senescence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study will provide mechanistic insight into how IPE influences macrophage\u2010driven inflammation in ASCVD and T2DM, informing strategies to target residual inflammatory risk in high\u2010risk cardiometabolic populations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dme.70247","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T06:04:56Z","timestamp":1770703496000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting inflammation in cardiometabolic disease: Icosapent ethyl modulates monocyte\u2010derived macrophages isolated from patients with cardiovascular disease with or without type 2 diabetes"],"prefix":"10.1111","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6058-3702","authenticated-orcid":false,"given":"J. 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U.","family":"Shah","sequence":"additional","affiliation":[{"name":"Lincolnshire Heart Centre United Lincolnshire Hospitals  Lincoln UK"},{"name":"Cardiology Department Hull University Teaching Hospitals  Hull UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Lee","sequence":"additional","affiliation":[{"name":"Cardiorenal Team, Diabetes, Metabolism &amp; Inflammation Group, College of Health and Science, Joseph Banks Laboratories University of Lincoln  Lincoln UK"},{"name":"Lincolnshire Heart Centre United Lincolnshire Hospitals  Lincoln UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4547-6777","authenticated-orcid":false,"given":"P. E.","family":"Squires","sequence":"additional","affiliation":[{"name":"Cardiorenal Team, Diabetes, Metabolism &amp; Inflammation Group, College of Health and Science, Joseph Banks Laboratories University of Lincoln  Lincoln UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. E.","family":"Hills","sequence":"additional","affiliation":[{"name":"Cardiorenal Team, Diabetes, Metabolism &amp; Inflammation Group, College of Health and Science, Joseph Banks Laboratories University of Lincoln  Lincoln UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.5334\/gh.1288"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-022-01516-6"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-025-02769-7"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.123.066213"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-023-01921-5"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2025.120411"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1812792"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2021.03.014"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2019.05.057"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.109104"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44319-024-00271-x"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.05.015"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(23)02399-9"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.111.960385"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2012.07.019"},{"issue":"1","key":"e_1_2_8_17_1","first-page":"11","article-title":"OxLDL induces the release of IL\u20101\u03b2 from primed human endothelial and smooth muscle cells via different caspase \u22121\u2010dependent mechanisms","volume":"4","author":"Almansouri M","year":"2022","journal-title":"Vasc Biol (Bristol, Engl)"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-85041-4"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/jimmun\/vkaf135"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1707914"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00520-1"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvae079"},{"key":"e_1_2_8_23_1","unstructured":"KDIGO.KDIGO Clinical Practice Guideline for Acute Kidney Injury 2022. 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