{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T05:03:24Z","timestamp":1777784604329,"version":"3.51.4"},"reference-count":46,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T00:00:00Z","timestamp":1738195200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"national institutes of health","doi-asserted-by":"publisher","award":["R21HL164436 (PGS, JG)"],"award-info":[{"award-number":["R21HL164436 (PGS, JG)"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Int J Artif Organs"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>as we look to extend ex vivo lung perfusion times (EVLP) to improve preservation, the metabolic activity of the lungs will require support from other organ functions. Active functional liver support, including detoxification, synthesis, and regulation, can improve lung preservation during EVLP. This study aimed to demonstrate the effects of hepatic conditioning of the EVLP perfusate on lung endothelium, via the receptor of advanced glycation end-products (RAGE)-nuclear-factor-\u03baB (NF-\u03baB) signaling in vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      we performed in vitro experiments using human lung microvascular endothelial cells (HLMVECs), human hepatocytes, and perfusate (Steen solution). Four experimental groups: 1) fresh Steen (negative controls, NC), 2) EVLP\u2019ed Steen control, this solution collected after 12\u2009h of EVLP of human lungs, 3) hepatocyte conditioned EVLP\u2019ed Steen (Hep-cond.), and 4) a RAGE inhibitor added in EVLP\u2019ed Steen (RAGE inhibitor). HLMVECs were incubated in each testing condition and exposed to hypoxia (1% O\n                      <jats:sub>2<\/jats:sub>\n                      \/8% CO\n                      <jats:sub>2<\/jats:sub>\n                      ) for 24\u2009h. Media were collected to investigate NF-\u03baB signaling and endothelial glycocalyx damage.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>HLMVECs incubated under hypoxia in EVLP\u2019ed Steen showed significantly upregulated NF-\u03baB signal and endothelial damage denoted by increased glycosaminoglycans and matrix metalloproteinase-2 activity among the groups. The Hep-cond. solution significantly attenuated those findings, while the RAGE inhibitor attenuated the NF-\u03baB signal but not endothelial glycocalyx damage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Our study demonstrates that hepatic function incorporated into EVLP can ameliorate pulmonary endothelial cells injury under hypoxic normothermic perfusion exposure. Our data supports the concept of incorporating other organ functions into an organ perfusion platform, to enhance lung graft preservation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03913988251315092","type":"journal-article","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:26:16Z","timestamp":1738283176000},"page":"84-91","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Hepatic conditioning results in better lung endothelial cell preservation under hypoxic environment in vitro"],"prefix":"10.1177","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8921-1944","authenticated-orcid":false,"given":"Kentaro","family":"Noda","sequence":"first","affiliation":[{"name":"Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center Health System, Pittsburgh, PA, 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