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dc.contributor.authorOskolkova, O.
dc.contributor.authorSarich, N.
dc.contributor.authorTian, Y.
dc.date.accessioned2019-06-05T18:28:13Z
dc.date.available2019-06-05T18:28:13Z
dc.date.issued2018
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85041402722&doi=10.1038%2fs41598-018-19197-1&partnerID=40&md5=c3f8c04cbfa2b6514728ede6a1684761
dc.identifier.urihttp://hdl.handle.net/10713/9400
dc.description.abstractCorrection of barrier dysfunction and inflammation in acute lung injury (ALI) represents an important problem. Previous studies demonstrate barrier-protective and anti-inflammatory effects of bioactive lipid prostacyclin and its stable analog iloprost (ILO). We generated a phospholipase resistant synthetic phospholipid with iloprost attached at the sn-2 position (ILO-PC) and investigated its biological effects. In comparison to free ILO, ILO-PC caused sustained endothelial cell (EC) barrier enhancement, linked to more prolonged activation of Rap1 and Rac1 GTPases and their cytoskeletal and cell junction effectors: cortactin, PAK1, p120-catenin and VE-cadherin. ILO and ILO-PC equally efficiently suppressed acute, Rho GTPase-dependent EC hyper-permeability caused by thrombin. However, ILO-PC exhibited more sustained barrier-protective and anti-inflammatory effects in the model of chronic EC dysfunction caused by bacterial wall lipopolysacharide (LPS). ILO-PC was also more potent inhibitor of NFκB signaling and lung vascular leak in the murine model of LPS-induced ALI. Treatment with ILO-PC showed more efficient ALI recovery over 3 days after LPS challenge than free ILO. In conclusion, this study describes a novel synthetic phospholipid with barrier-enhancing and anti-inflammatory properties superior to existing prostacyclin analogs, which may be used as a prototype for future development of more efficient treatment for ALI and other vascular leak syndromes. Copyright 2018 The Author(s).en_US
dc.description.urihttps://dx.doi.org/10.1038/s41598-018-19197-1en_US
dc.language.isoen-USen_US
dc.publisherNature Publishing Groupen_US
dc.relation.ispartofScientific Reports
dc.subject.meshEndothelium, Vascularen_US
dc.subject.meshIloprost--therapeutic useen_US
dc.subject.meshLungen_US
dc.titleIncorporation of iloprost in phospholipase-resistant phospholipid scaffold enhances its barrier protective effects on pulmonary endotheliumen_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s41598-018-19197-1
dc.identifier.pmid29343759


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