{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T12:59:36Z","timestamp":1791809976826,"version":"4.3.4"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T00:00:00Z","timestamp":1744848000000},"content-version":"vor","delay-in-days":47,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Xenotransplantation, the transplantation of organs from pigs to humans, presents significant challenges due to immune rejection, which is driven by molecular incompatibilities between species. This study investigates the compatibility between human thrombin and porcine protease\u2010activated receptor\u20101 (PAR\u20101), a key regulator of both coagulation and inflammatory responses. Human thrombin activates PAR\u20101 in human vascular endothelial cells, but our results demonstrate that human thrombin does not effectively activate PAR\u20101 in porcine vascular endothelial cells due to differences in amino acid sequences, particularly at the thrombin cleavage site and the Hir domain. Protein\u2010protein docking analysis further reveals that porcine PAR\u20101 forms less stable interactions with human thrombin compared to human PAR\u20101, resulting in reduced activation. This molecular incompatibility likely contributes to impaired nitric oxide (NO) production, endothelial dysfunction, and increased inflammation, which are critical for the survival of transplanted organs. Additionally, experiments using the PAR\u20101 inhibitor vorapaxar (Vor) show that inhibiting PAR\u20101 signaling can suppress inflammatory cytokine and chemokine expression in co\u2010cultures of human macrophages and porcine endothelial cells. These findings suggest that selective PAR\u20101 inhibitors or targeted therapies regulating thrombin\u2010PAR\u20101 signaling may improve the success rate of xenotransplantation. However, further in vivo studies are needed to validate these findings and explore therapeutic interventions targeting thrombin\u2010PAR\u20101 interactions to enhance xenograft survival.<\/jats:p>","DOI":"10.1111\/xen.70041","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T08:39:11Z","timestamp":1744879151000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Defect in Sensing Human Thrombin by Porcine Endothelial Protease\u2010Activated Receptor\u20101: Molecular Incompatibility Between Porcine PAR\u20101 and Human Thrombin"],"prefix":"10.1111","volume":"32","author":[{"given":"Thi Xoan","family":"Hoang","sequence":"first","affiliation":[{"name":"Department of Life Science Gachon University  Seongnam Kyeonggi South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju\u2010Young","family":"Bang","sequence":"additional","affiliation":[{"name":"Department of Life Science Gachon University  Seongnam Kyeonggi South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinh Phuoc","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Life Science Gachon University  Seongnam Kyeonggi South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phu Chi","family":"Vu","sequence":"additional","affiliation":[{"name":"Department of Life Science Gachon University  Seongnam Kyeonggi South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ik Jin","family":"Yun","sequence":"additional","affiliation":[{"name":"Department of Surgery Konkuk University School of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee Jung","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Hallym University College of Medicine  Anyang South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Life Science Gachon University  Seongnam Kyeonggi South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.53.082901.103900"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-995828"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2008.02210.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.20.9208"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0801082"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/bmb\/ldx043"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/29325"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/35007085"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-008-7555-y"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.9.6580"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2005.07.041"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/353674a0"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2003.11.008"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M608288200"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphs.2022.02.001"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00372.2003"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.6.3301"},{"issue":"11","key":"e_1_2_8_19_1","first-page":"3685","article-title":"Monocyte Arrest and Transmigration on Inflamed Endothelium in Shear Flow Is Inhibited by Adenovirus\u2010Mediated Gene Transfer of I\u03baB\u2010 \u03b1. 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