BACKGROUND: as we look to extend METHODS: 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'ed Steen control, this solution collected after 12 h of EVLP of human lungs, 3) hepatocyte conditioned EVLP'ed Steen (Hep-cond.), and 4) a RAGE inhibitor added in EVLP'ed Steen (RAGE inhibitor). HLMVECs were incubated in each testing condition and exposed to hypoxia (1% O RESULTS: HLMVECs incubated under hypoxia in EVLP'ed Steen showed significantly upregulated NF-κB 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-κB signal but not endothelial glycocalyx damage. CONCLUSION: 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.