{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T18:30:20Z","timestamp":1793212220912,"version":"4.5.0"},"reference-count":54,"publisher":"American Society for Clinical Investigation","issue":"5","license":[{"start":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T00:00:00Z","timestamp":1646697600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"crossref","award":["FS\/18\/45\/33862"],"award-info":[{"award-number":["FS\/18\/45\/33862"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,8]]},"abstract":"<jats:p>Following myocardial infarction (MI), elderly patients have a poorer prognosis than younger patients, which may be linked to increased coronary microvessel susceptibility to injury. Interleukin-36 (IL-36), a newly discovered proinflammatory member of the IL-1 superfamily, may mediate this injury, but its role in the injured heart is currently not known. We first demonstrated the presence of IL-36(\u03b1\/\u03b2) and its receptor (IL-36R) in ischemia\/reperfusion-injured (IR-injured) mouse hearts and, interestingly, noted that expression of both increased with aging. An intravital model for imaging the adult and aged IR-injured beating heart in real time in vivo was used to demonstrate heightened basal and injury-induced neutrophil recruitment, and poorer blood flow, in the aged coronary microcirculation when compared with adult hearts. An IL-36R antagonist (IL-36Ra) decreased neutrophil recruitment, improved blood flow, and reduced infarct size in both adult and aged mice. This may be mechanistically explained by attenuated endothelial oxidative damage and VCAM-1 expression in IL-36Ra\u2013treated mice. Our findings of an enhanced age-related coronary microcirculatory dysfunction in reperfused hearts may explain the poorer outcomes in elderly patients following MI. Since targeting the IL-36\/IL-36R pathway was vasculoprotective in aged hearts, it may potentially be a therapy for treating MI in the elderly population.<\/jats:p>","DOI":"10.1172\/jci.insight.155236","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T12:00:54Z","timestamp":1643889654000},"source":"Crossref","is-referenced-by-count":35,"title":["Targeting IL-36 improves age-related coronary microcirculatory dysfunction and attenuates myocardial ischemia\/reperfusion injury in mice"],"prefix":"10.1172","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2336-7417","authenticated-orcid":true,"given":"Juma","family":"El-Awaisi","sequence":"first","affiliation":[{"name":"Microcirculation Research Group, Institute of Cardiovascular Sciences, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9459-1494","authenticated-orcid":true,"given":"Dean P.J.","family":"Kavanagh","sequence":"additional","affiliation":[{"name":"Microcirculation Research Group, Institute of Cardiovascular Sciences, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8741-8466","authenticated-orcid":true,"given":"Marco R.","family":"Rink","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9651-1264","authenticated-orcid":true,"given":"Chris J.","family":"Weston","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9012-6683","authenticated-orcid":true,"given":"Nigel E.","family":"Drury","sequence":"additional","affiliation":[{"name":"Microcirculation Research Group, Institute of Cardiovascular Sciences, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2960-7829","authenticated-orcid":true,"given":"Neena","family":"Kalia","sequence":"additional","affiliation":[{"name":"Microcirculation Research Group, Institute of Cardiovascular Sciences, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2022,3,8]]},"reference":[{"issue":"4","key":"B1","doi-asserted-by":"crossref","first-page":"162663","DOI":"10.1016\/j.ahj.2011.08.002","article-title":"Incidence and predictors of heart failure following percutaneous coronary intervention in ST-segment elevation myocardial infarction: the HORIZONS-AMI trial","volume":"162","author":"Kelly","year":"2011","journal-title":"Am Heart J"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI62874"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra061889"},{"issue":"8","key":"B4","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1177\/014107680209500805","article-title":"Myocardial infarction with angiographically normal coronary arteries","volume":"95","author":"Chandrasekaran","year":"2002","journal-title":"J R Soc Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2011.04.010"},{"issue":"6","key":"B6","first-page":"843","article-title":"Aging increases ischemia-reperfusion injury in the isolated, buffer-perfused heart","volume":"6","author":"Lesnefsky","year":"1994","journal-title":"J Lab Clin Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(01)01432-2"},{"issue":"9","key":"B8","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1016\/j.exger.2004.06.006","article-title":"Cardioprotection with cariporide, a sodium-proton exchanger inhibitor, after prolonged ischemia and reperfusion in senescent rats","volume":"9","author":"Besse","year":"2004","journal-title":"Exp Gerontol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00054.2013"},{"key":"B10","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1111\/j.1749-6632.2000.tb06651.x","article-title":"Inflamm-aging. 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