{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T16:41:44Z","timestamp":1787676104458,"version":"build-2784847793"},"reference-count":56,"publisher":"Portland Press Ltd.","issue":"10","license":[{"start":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T00:00:00Z","timestamp":1715558400000},"content-version":"vor","delay-in-days":12,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["388364"],"award-info":[{"award-number":["388364"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,5,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Aim: Acute kidney injury (AKI) increases the risk for progressive chronic kidney disease (CKD). MicroRNA (miR)-486-5p protects against kidney ischemia\u2013reperfusion (IR) injury in mice, although its long-term effects on the vasculature and development of CKD are unknown. We studied whether miR-486-5p would prevent the AKI to CKD transition in rat, and affect vascular function. Methods: Adult male rats were subjected to bilateral kidney IR followed by i.v. injection of liposomal-packaged miR-486-5p (0.5 mg\/kg). Kidney function and histologic injury were assessed after 24 h and 10 weeks. Kidney endothelial protein levels were measured by immunoblot and immunofluorescence, and mesenteric artery reactivity was determined by wire myography. Results: In rats with IR, miR-486-5p blocked kidney endothelial cell increases in intercellular adhesion molecule-1 (ICAM-1), reduced neutrophil infiltration and histologic injury, and normalized plasma creatinine (P&amp;lt;0.001). However, miR-486-5p attenuated IR-induced kidney endothelial nitric oxide synthase (eNOS) expression (P&amp;lt;0.05). At 10 weeks, kidneys from rats with IR alone had decreased peritubular capillary density and increased interstitial collagen deposition (P&amp;lt;0.0001), and mesenteric arteries showed impaired endothelium-dependent vasorelaxation (P&amp;lt;0.001). These changes were inhibited by miR-486-5p. Delayed miR-486-5p administration (96 h, 3 weeks after IR) had no impact on kidney fibrosis, capillary density, or endothelial function. Conclusion: In rats, administration of miR-486-5p early after kidney IR prevents injury, and protects against CKD development and systemic endothelial dysfunction. These protective effects are associated with inhibition of endothelial ICAM-1 and occur despite reduction in eNOS. miR-486-5p holds promise for the prevention of ischemic AKI and its complications.<\/jats:p>","DOI":"10.1042\/cs20231752","type":"journal-article","created":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T11:59:19Z","timestamp":1715601559000},"page":"599-614","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["miR-486-5p protects against rat ischemic kidney injury and prevents the transition to chronic kidney disease and vascular dysfunction"],"prefix":"10.1042","volume":"138","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9578-9785","authenticated-orcid":false,"given":"Adrianna","family":"Douvris","sequence":"first","affiliation":[{"name":"1Division of Nephrology, Department of Medicine and Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa and the Ottawa Hospital, Ottawa, Canada"},{"name":"2Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7770-7133","authenticated-orcid":false,"given":"Jose\u00a0L.","family":"Vi\u00f1as","sequence":"additional","affiliation":[{"name":"1Division of Nephrology, Department of Medicine and Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa and the Ottawa Hospital, Ottawa, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6251-1338","authenticated-orcid":false,"given":"Alexey","family":"Gutsol","sequence":"additional","affiliation":[{"name":"1Division of Nephrology, Department of Medicine and Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa and the Ottawa Hospital, Ottawa, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Zimpelmann","sequence":"additional","affiliation":[{"name":"1Division of Nephrology, Department of Medicine and Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa and the Ottawa Hospital, Ottawa, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3951-2911","authenticated-orcid":false,"given":"Dylan","family":"Burger","sequence":"additional","affiliation":[{"name":"1Division of Nephrology, Department of Medicine and Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa and the Ottawa Hospital, Ottawa, Canada"},{"name":"2Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1482-5826","authenticated-orcid":false,"given":"Kevin\u00a0D.","family":"Burns","sequence":"additional","affiliation":[{"name":"1Division of Nephrology, Department of Medicine and Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa and the Ottawa Hospital, Ottawa, Canada"},{"name":"2Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2024,5,22]]},"reference":[{"key":"2024052210055111500_B1","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1159\/000337487","article-title":"Acute kidney injury and mortality in hospitalized patients","volume":"35","author":"Wang","year":"2012","journal-title":"Am. 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