{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T13:03:20Z","timestamp":1791810200252,"version":"4.3.4"},"reference-count":57,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,11,5]],"date-time":"2013-11-05T00:00:00Z","timestamp":1383609600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Coagulation disorders remain barriers to successful pig\u2010to\u2010primate organ xenotransplantation. In vitro, we investigated the impact of pig genetic modifications on human platelet aggregation in response to pig aortic endothelial cells (<jats:styled-content style=\"fixed-case\">pAEC<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In comparison to human (h)AEC and wild\u2010type (WT) <jats:styled-content style=\"fixed-case\">pAEC<\/jats:styled-content>, the expression of human complement\u2010 (CD46, CD55) or coagulation (thrombomodulin [TBM], endothelial protein C receptor [EPCR]) \u2010regulatory proteins on <jats:styled-content style=\"fixed-case\">pAEC<\/jats:styled-content> from WT or \u03b11,3\u2010galactosyltransferase gene\u2010knockout (GTKO) pigs was studied by flow cytometry. Using platelet\u2010aggregometry, human whole blood platelet aggregation was evaluated after co\u2010incubation with various AEC. Further, the inhibitory effect on aggregation of heparin, low molecular weight heparin, and hirudin was assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Heparin, low molecular weight heparin and hirudin almost completely prevented platelet aggregation induced by WT <jats:styled-content style=\"fixed-case\">pAEC<\/jats:styled-content>. The level of expression of human CD46, CD55, TBM and EPCR on <jats:styled-content style=\"fixed-case\">pAEC<\/jats:styled-content> was comparable to that on <jats:styled-content style=\"fixed-case\">hAEC<\/jats:styled-content>. Platelet aggregation induced by all genetically modified <jats:styled-content style=\"fixed-case\">pAEC<\/jats:styled-content> was significantly less (P\u00a0&lt;\u00a00.05) than that by WT <jats:styled-content style=\"fixed-case\">pAEC<\/jats:styled-content> (which was 54%). GTKO\/CD46\/TBM <jats:styled-content style=\"fixed-case\">pAEC<\/jats:styled-content> induced the least platelet aggregation (27%)\u2014a reduction of almost 50%\u2014but this remained significantly greater (P\u00a0&lt;\u00a00.01) than aggregation induced by <jats:styled-content style=\"fixed-case\">hAEC<\/jats:styled-content> (4%). There was significant positive correlation between reduction of aggregation and TBM or EPCR expression on <jats:styled-content style=\"fixed-case\">pAEC<\/jats:styled-content> (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.89 and <jats:italic>r<\/jats:italic>\u00a0=\u00a00.86, respectively; P\u00a0&lt;\u00a00.05). Platelet aggregation induced by GTKO\/CD46\/TBM <jats:styled-content style=\"fixed-case\">pAEC<\/jats:styled-content> in the presence of hirudin (1\u00a0IU\/ml) was comparable to platelet aggregation induced by <jats:styled-content style=\"fixed-case\">hAEC<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Genetic modification of <jats:styled-content style=\"fixed-case\">pAEC<\/jats:styled-content> is associated with significant reduction of human platelet aggregation in vitro. With concomitant thrombin inhibition, platelet aggregation was comparable to that stimulated by <jats:styled-content style=\"fixed-case\">hAEC<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/xen.12073","type":"journal-article","created":{"date-parts":[[2013,11,5]],"date-time":"2013-11-05T09:20:17Z","timestamp":1383643217000},"page":"72-83","source":"Crossref","is-referenced-by-count":66,"title":["Regulation of human platelet aggregation by genetically modified pig endothelial cells and thrombin inhibition"],"prefix":"10.1111","volume":"21","author":[{"given":"Hayato","family":"Iwase","sequence":"first","affiliation":[{"name":"Thomas E. Starzl Transplantation Institute University of Pittsburgh Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burcin","family":"Ekser","sequence":"additional","affiliation":[{"name":"Thomas E. Starzl Transplantation Institute University of Pittsburgh Pittsburgh PA USA"},{"name":"Department of Surgery, Transplantation and Advanced Technologies Vascular Surgery and Organ Transplant Unit University Hospital of Catania Catania Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetaka","family":"Hara","sequence":"additional","affiliation":[{"name":"Thomas E. Starzl Transplantation Institute University of Pittsburgh Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Phelps","sequence":"additional","affiliation":[{"name":"Revivicor Inc. Blacksburg VA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Ayares","sequence":"additional","affiliation":[{"name":"Revivicor Inc. Blacksburg VA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David K.C.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Thomas E. 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